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19<meta name="citation_author_institution" content="Institute of New Frontier Research, Hallym University College of Medicine, Chuncheon,">
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446<div class="article-contrib">
447<span class="capture-id"><span id="ORCID_0000-0001-7132-3921" class="ORCID"><a href="ORCID/0000-0001-7132-3921">Md Hasanuzzaman</a></span><a href="https://orcid.org/0000-0001-7132-3921" target="_blank"><img style="vertical-align:middle; margin-left:0.2em; margin-right:0.05em; padding-bottom: 0.5em;" src="/image/icon-orcid.jpg"></a>,<sup>1</sup><sup>,</sup><sup>*</sup></span>
448<span class="capture-id"><span id="ORCID_0000-0003-4908-5431" class="ORCID"><a href="ORCID/0000-0003-4908-5431">Chang Seok Bang</a></span><a href="https://orcid.org/0000-0003-4908-5431" target="_blank"><img style="vertical-align:middle; margin-left:0.2em; margin-right:0.05em; padding-bottom: 0.5em;" src="/image/icon-orcid.jpg"></a>,<sup>1</sup><sup>,</sup><sup>2</sup><sup>,</sup><sup>*</sup></span>
449<span class="capture-id"><span id="ORCID_0000-0002-5418-500X" class="ORCID"><a href="ORCID/0000-0002-5418-500X">Jae Jun Lee</a></span><a href="https://orcid.org/0000-0002-5418-500X" target="_blank"><img style="vertical-align:middle; margin-left:0.2em; margin-right:0.05em; padding-bottom: 0.5em;" src="/image/icon-orcid.jpg"></a>,<span class="article-icon-corresp"></span><sup>1</sup><sup>,</sup><sup>3</sup></span>
450 and <span class="capture-id"><span id="ORCID_0000-0003-3996-3472" class="ORCID"><a href="ORCID/0000-0003-3996-3472">Eun Jeong Gong</a></span><a href="https://orcid.org/0000-0003-3996-3472" target="_blank"><img style="vertical-align:middle; margin-left:0.2em; margin-right:0.05em; padding-bottom: 0.5em;" src="/image/icon-orcid.jpg"></a><span class="article-icon-corresp"></span><sup>1</sup><sup>,</sup><sup>2</sup></span>
451</div>
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460<li>
461<sup>1</sup>Institute of New Frontier Research, Hallym University College of Medicine, Chuncheon, Korea.<br>
462</li>
463<li>
464<sup>2</sup>Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea.<br>
465</li>
466<li>
467<sup>3</sup>Department of Anesthesiology and Pain Medicine, Hallym University College of Medicine, Chuncheon, Korea.<br>
468</li>
469</ul></div></li>
470<li class="list-group-item"><div class="article-author-notes"><span class="capture-id"><div>
471<span class="gen"></span><span class="article-icon-corresp"></span>Address for Correspondence: Eun Jeong Gong, MD, PhD. Department of Internal Medicine, Hallym University College of Medicine, 77 Sakju-ro, Chuncheon 24253, Republic of Korea; Institute of New Frontier Research, Hallym University College of Medicine, 1 Hallymdaehak-gil, Chuncheon 24252, Republic of Korea. <span class="author-email">
471Email: <A href="mailto:[email protected]">[email protected]</A></span>
472
473</div>
474<div>
475<span class="gen"></span><span class="article-icon-corresp"></span>Address for Correspondence: Jae Jun Lee, MD, PhD. Department of Anesthesiology and Pain Medicine, Hallym University College of Medicine, 77 Sakju-ro, Chuncheon 24253, Republic of Korea; Institute of New Frontier Research, Hallym University College of Medicine, 1 Hallymdaehak-gil, Chuncheon 24252, Republic of Korea. <span class="author-email">Email: <A href="mailto:[email protected]">[email protected]</A></span>
476
477</div>
478<div class="fm-footnote" id="FN1"><div class="p p-first"><span class="capture-id"><p></p>
479<sup>*</sup>Md Hasanuzzaman and Chang Seok Bang contributed equally to this work.</span></div></div></span></div></li>
480</ul></div></div>
481<div class="collapse multi-collapse" id="article-front-meta-id-articlehistory"><div class="card card-body"><div class="article-received-accepted-date">Received May 15, 2026; Accepted  August 18, 2026.</div></div></div>
482<div class="collapse multi-collapse" id="article-front-meta-id-license"><div class="card card-body"><div class="article-license">
483<p>This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (<a href="https://creativecommons.org/licenses/by-nc/4.0/" target="_blank">https://creativecommons.org/licenses/by-<wbr/>nc/4.0/</a>) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.</p>
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485<div id="article-citedby"></div>
486<div id="article-relate-articles"></div>
487</div>
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490<div><div class="article-abstract">
491<div class="article-section-header">
492<div class="__SECTION__" id="__ID_SECTION_0" data-section-name="Abstract"><div class="dropdown">
493<a href="#" class="dropdown-goto dropdown-toggle d-none" id="dropdownGoto_0" title="Go to other sections in this page" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">Go to:</a><div class="dropdown-menu dropdown-menu-right d-none" aria-labelledby="dropdownGoto_0"></div>
494</div></div>
495<h2>Abstract</h2>
496</div>
497<p>Fecal microbiota transplantation (FMT) has emerged as a transformative therapeutic approach to restore gut microbial homeostasis. The most established indication is recurrent <i>Clostridioides difficile</i> infection (CDI), demonstrating that restoring ecosystem-level microbiota has substantial clinical benefits. Building on this success, FMT is now being investigated across a broader range of indications associated with gut dysbiosis and altered microbiome-host signaling, including inflammatory bowel disease, irritable bowel syndrome, metabolic, and neurological disorders. Mechanistic insights into the gut–organ axes provide biological plausibility for this expansion; gut dysbiosis can function as a modifiable upstream driver of host metabolism, immune–neural signaling, and barrier function. However, the clinical benefits beyond CDI remain heterogeneous and often modest, highlighting the need for further research on patient stratification, standardized protocols, and mechanistic biomarkers. Furthermore, regulatory frameworks remain heterogeneous worldwide, and recent approvals of standardized microbiota-based products for recurrent CDI represent a transition toward treating microbiome therapeutics as regulated biologics. This review synthesizes the mechanistic rationale and current evidence for FMT beyond CDI and outlines future directions for personalized and next-generation microbiome therapeutics.</p>
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500<div><div class="article-abstract">
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502<div class="__SECTION__" id="__ID_SECTION_1" data-section-name="Graphical Abstract"><div class="dropdown">
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504</div></div>
505<h2>Graphical Abstract</h2>
506</div></div>
507
508<p>
509<img class="img-fluid" src="/ArticleImage/0063JKMS/jkms-41-e335-abf001.jpg"></p>
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515<div id="article-level-0-end-metadata" class="fm">
516<div class="my-3"><div>
517<div class="article-keyword-group-title">Keywords</div>
518<div>
519<span class="capture-id">Fecal Microbiota Transplantation</span>; <span class="capture-id">Inflammatory Bowel Diseases</span>; <span class="capture-id">Metabolic Diseases</span>; <span class="capture-id">Neuroinflammatory Diseases</span>
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529<div class="__SECTION__" id="__ID_SECTION_2" data-section-name="INTRODUCTION"><div class="dropdown">
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531</div></div>
532<h2>INTRODUCTION</h2>
533</div></div>
534<p>The human gut microbiota is a diverse community of microorganisms that plays a crucial role in maintaining gastrointestinal (GI) health.<span class="xref"><span id="XREF_B1" class="ref-destination-back"></span><a href="#B1" data-id="XREF_B1" data-toggle="ref-popover" data-trigger="manual" data-placement="right">1</a></span> Comprising bacteria, viruses, fungi, and archaea, the gut microbiota contributes to various physiological functions, including digestion and metabolism, fermentation of dietary substrates, vitamin production, immune development, and protection against pathogens.<span class="xref"><span id="XREF_B2" class="ref-destination-back"></span><a href="#B2" data-id="XREF_B2" data-toggle="ref-popover" data-trigger="manual" data-placement="right">2</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B3" class="ref-destination-back"></span><a href="#B3" data-id="XREF_B3" data-toggle="ref-popover" data-trigger="manual" data-placement="right">3</a></span> High overall microbial diversity, stability, and redundancy of key microbial functions have been established as markers of a healthy gut microbiota. In contrast, disruption of this ecosystem and dysbiosis has been linked to a spectrum of GI disorders, including <i>Clostridioides difficile</i> infection (CDI), inflammatory bowel disease (IBD), colorectal cancer, and disorders of gut–brain interactions, such as irritable bowel syndrome (IBS).<span class="xref"><span id="XREF_B4" class="ref-destination-back"></span><a href="#B4" data-id="XREF_B4" data-toggle="ref-popover" data-trigger="manual" data-placement="right">4</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B5" class="ref-destination-back"></span><a href="#B5" data-id="XREF_B5" data-toggle="ref-popover" data-trigger="manual" data-placement="right">5</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B6" class="ref-destination-back"></span><a href="#B6" data-id="XREF_B6" data-toggle="ref-popover" data-trigger="manual" data-placement="right">6</a></span> Accumulating evidence supports the involvement of the microbiota in systemic diseases through interconnected gut–organ axes, including the gut–brain, gut–liver, and gut–immune pathways.<span class="xref"><span id="XREF_B7" class="ref-destination-back"></span><a href="#B7" data-id="XREF_B7" data-toggle="ref-popover" data-trigger="manual" data-placement="right">7</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B8" class="ref-destination-back"></span><a href="#B8" data-id="XREF_B8" data-toggle="ref-popover" data-trigger="manual" data-placement="right">8</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B9" class="ref-destination-back"></span><a href="#B9" data-id="XREF_B9" data-toggle="ref-popover" data-trigger="manual" data-placement="right">9</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B10" class="ref-destination-back"></span><a href="#B10" data-id="XREF_B10" data-toggle="ref-popover" data-trigger="manual" data-placement="right">10</a></span></p>
535<p>Fecal microbiota transplantation (FMT), defined as the transfer of stool-derived microbial communities from a healthy donor to a recipient, has emerged as a promising intervention to restore microbial balance (<span class="fig-table-link"><a href="#F1">Fig. 1</a></span>
535).<span class="xref"><span id="XREF_B11" class="ref-destination-back"></span><a href="#B11" data-id="XREF_B11" data-toggle="ref-popover" data-trigger="manual" data-placement="right">11</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B12" class="ref-destination-back"></span><a href="#B12" data-id="XREF_B12" data-toggle="ref-popover" data-trigger="manual" data-placement="right">12</a></span> FMT can be administered via the upper GI route (using oral capsules, upper endoscopy, or naso-enteric tubes); the lower GI route (via colonoscopy, sigmoidoscopy, or enema); or a combination of both approaches.<span class="xref"><span id="XREF_B13" class="ref-destination-back"></span><a href="#B13" data-id="XREF_B13" data-toggle="ref-popover" data-trigger="manual" data-placement="right">13</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B14" class="ref-destination-back"></span><a href="#B14" data-id="XREF_B14" data-toggle="ref-popover" data-trigger="manual" data-placement="right">14</a></span> FMT aims to ameliorate the dysbiotic state by increasing overall diversity and restoring microbiota function. The gut microbiota affects host physiology through several pathways: i) production of microbial metabolites, such as short-chain fatty acids (SCFAs), bile acid derivatives, and tryptophan metabolites, ii) maintenance of intestinal barrier integrity and control of endotoxemia, and iii) bidirectional communication with the nervous and immune systems.<span class="xref"><span id="XREF_B11" class="ref-destination-back"></span><a href="#B11" data-id="XREF_B11" data-toggle="ref-popover" data-trigger="manual" data-placement="right">11</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B15" class="ref-destination-back"></span><a href="#B15" data-id="XREF_B15" data-toggle="ref-popover" data-trigger="manual" data-placement="right">15</a></span> In this context, FMT represents a high-intensity intervention capable of shifting microbial community structure and function.<div class="image-at-section"></div></p>
536<p><div class="article-fig image-at-section"><div class="article-figure-table" id="F1"><div class="article-figure-table-card" id="FIGURE-F1" data-type="F" data-afn="63_JKMS_41_38_e335" data-fn="jkms-41-e335-g001_0063JKMS"><div class="card border-0 my-3"><div class="row no-gutters">
537<div class="col-md-4 mx-auto d-flex justify-content-center flex-wrap align-middle"><div class="card-body">
538<a href="#" class="article-figure-table-btn" data-type="F"><img class="align-top" src="/ArticleImage/0063JKMS/jkms-41-e335-g001-m.jpg"></a>
539</div></div>
540<div class="col-md-8"><div class="card-body">
541<p class="card-text"><span class="label"><a href="#" class="article-figure-table-btn" data-type="F">Fig. 1</a>
542</span><span class="capture-id"><br><span class="capture-id">Overview of FMT and its multifaceted outcomes. The schematic illustrates the sequential process of FMT from donor to recipient. The gastrointestinal tract of a healthy donor harbors a diverse community of commensal microorganisms, as depicted in the magnified inset, which shows a rich consortium of bacterial species with varying morphologies. This microbiota produces a wide range of functional molecules, including bacterial products, metabolic precursors, neurotransmitters, neuroactive metabolites, bioactive molecules, and immune signaling mediators. The fecal material from the healthy donor undergoes standardized preparation procedures, including filtration, dilution, and encapsulation, to generate the transplant material. The processed fecal microbiota is administered to the recipient, whose gut microbial community is represented prior to engraftment. Following FMT, the recipient's gut ecosystem is remodeled, exhibiting increased microbial diversity and richness along with the restoration of key metabolic pathways and bioactive metabolite production. The figure was created via BioRender.com.</span><br><span class="capture-id">FMT = fecal microbiota transplantation.</span></span></p>
543<ul class="list-inline">
544<li class="list-inline-item">
544<a role="button" class="btn btn-outline-article btn-sm article-figure-table-btn" data-type="F">Click for larger image</a></li>
545<li class="list-inline-item"><a role="button" class="btn btn-outline-article btn-sm" href="ViewImagePopup.php?Type=FP&amp;id=F1&amp;afn=63_JKMS_41_38_e335&amp;fn=jkms-41-e335-g001_0063JKMS" target="_blank">Download as PowerPoint slide</a></li>
546</ul>
547</div></div>
548</div></div></div></div></div></p>
549<p>The clinical effects of FMT are most clearly demonstrated in recurrent <i>Clostridioides difficile</i> infection (rCDI), where it achieves resolution rates exceeding 80% in patients with multiple relapses.<span class="xref"><span id="XREF_B16" class="ref-destination-back"></span><a href="#B16" data-id="XREF_B16" data-toggle="ref-popover" data-trigger="manual" data-placement="right">16</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B17" class="ref-destination-back"></span><a href="#B17" data-id="XREF_B17" data-toggle="ref-popover" data-trigger="manual" data-placement="right">17</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B18" class="ref-destination-back"></span><a href="#B18" data-id="XREF_B18" data-toggle="ref-popover" data-trigger="manual" data-placement="right">18</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B19" class="ref-destination-back"></span><a href="#B19" data-id="XREF_B19" data-toggle="ref-popover" data-trigger="manual" data-placement="right">19</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B20" class="ref-destination-back"></span><a href="#B20" data-id="XREF_B20" data-toggle="ref-popover" data-trigger="manual" data-placement="right">20</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B21" class="ref-destination-back"></span><a href="#B21" data-id="XREF_B21" data-toggle="ref-popover" data-trigger="manual" data-placement="right">21</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B22" class="ref-destination-back"></span><a href="#B22" data-id="XREF_B22" data-toggle="ref-popover" data-trigger="manual" data-placement="right">22</a></span> This success has established the broader principle that targeted restoration of the gut ecosystem could yield significant clinical benefits. This has prompted interest in whether microbiome modulation can be therapeutic in other diseases where dysbiosis contributes to pathophysiology, such as metabolic disorders characterized by insulin resistance and chronic inflammation, and neurological disorders linked to gut–brain signaling.<span class="xref"><span id="XREF_B23" class="ref-destination-back"></span><a href="#B23" data-id="XREF_B23" data-toggle="ref-popover" data-trigger="manual" data-placement="right">23</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B24" class="ref-destination-back"></span><a href="#B24" data-id="XREF_B24" data-toggle="ref-popover" data-trigger="manual" data-placement="right">24</a></span> However, the clinical translation of FMT beyond CDI remains challenging because of substantial heterogeneity in donor selection, recipient characteristics, administration protocols, outcome measures, and durability of response. Therefore, this narrative review aimed to synthesize the expanding clinical landscape of FMT beyond rCDI, with an emphasis on i) the current evidence and mechanistic pathways supporting the expansion into IBD, IBS, metabolic, and neurologic disorders and ii) practical considerations, including safety, standardization, and evolving regulatory frameworks. By synthesizing the current literature, we provide researchers with the current state of evidence and outline future research directions in this rapidly evolving field.</p>
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552<div>
553<div><div class="article-section-header">
554<div class="__SECTION__" id="__ID_SECTION_3" data-section-name="METHODS"><div class="dropdown">
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556</div></div>
557<h2>METHODS</h2>
558</div></div>
559<p>We conducted a comprehensive narrative review of FMT for indications beyond CDI. PubMed, EMBASE, and the Cochrane Library were searched using combinations of the terms “fecal microbiota transplantation,” “inflammatory bowel diseases,” “irritable bowel syndrome,” “metabolic 
559syndrome,” “obesity,” “diabetes mellitus,” “insulin resistance,” “non-alcoholic fatty liver disease,” “Parkinson disease,” “multiple sclerosis,” “Alzheimer disease,” “amyotrophic lateral sclerosis,” “cognitive dysfunction,” through December 31, 2025. References from key articles were also manually screened to identify additional relevant studies. After identifying FMT-related literature, we focused on indications beyond CDI while including landmark CDI studies as comparative references.</p>
560<p>We prioritized current guidelines and consensus statements, recent systematic reviews and meta-analyses, randomized controlled trials (RCTs), and pivotal mechanistic studies. Studies were selected according to their methodological quality, clinical relevance, and contribution to understanding the mechanisms, efficacy, safety, and regulatory aspects of FMT. For the appraisal of clinical efficacy beyond <i>C. difficile</i> infection, we focused on RCTs of donor-derived FMT in the predefined indications addressed in this review (IBD, IBS, metabolic and neurological disorders). When FMT was combined with a co-intervention, a trial was included only if the comparator arm shared the same co-intervention, so that two arms differed by FMT alone and its effect could be isolated. The exclusion criteria were manuscripts not written in English or Korean, in vitro studies, and studies conducted on pediatric or adolescent populations. We additionally excluded single-arm (uncontrolled) studies and trials of autologous FMT as the intervention when used for efficacy claims, as well as indications outside the predefined scope (e.g., pouchitis and hepatic encephalopathy). Conference abstracts, posters, and preprints were also excluded from final selection. As this review was designed as a narrative review rather than a systematic review, a Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology was not applied; however, literature selection was performed transparently by two authors (Hasanuzzaman M and Gong EJ) to provide a balanced overview of the current evidence while acknowledging areas of uncertainty and heterogeneity.</p>
561<p>Certainty of evidence for each indication was appraised using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework, applied separately to each clinically relevant outcome (induction and maintenance of remission for IBD, symptom response for IBS, and metabolic and clinical endpoints for metabolic disorders).<span class="xref"><span id="XREF_B25" class="ref-destination-back"></span><a href="#B25" data-id="XREF_B25" data-toggle="ref-popover" data-trigger="manual" data-placement="right">25</a></span> Because the efficacy evidence comprised RCTs, each outcome began at high certainty and was rated down for risk of bias (e.g., open-label design, use of autologous FMT as the comparator, premature termination for futility, and small pilot samples), inconsistency (discordant direction or magnitude of effect across trials), indirectness (reliance on surrogate endpoints such as microbial engraftment or biomarker changes rather than patient-important outcomes), imprecision (small samples, few events, or wide confidence intervals), and suspected publication bias. Ulcerative colitis (UC) and Crohn’s disease (CD) were graded separately rather than as a single IBD category, and neurological indications were distinguished by disease. The resulting certainty ratings (high, moderate, low, or very low) were additionally summarized as pragmatic translational-readiness tiers (established, emerging-effective, emerging-inconsistent, and exploratory or insufficient) to convey clinical maturity (<span class="fig-table-link"><a href="#S1">Supplementary Tables 1</a></span> and <span class="fig-table-link"><a href="#S2">2</a></span><span class="gen">, </span><span class="fig-table-link"><a href="#F2">Fig. 2</a></span>); indications were rated down not for an absence of trials but for inconsistent effects or benefits limited to surrogate endpoints.<div class="image-at-section"></div></p>
562<p><div class="article-fig image-at-section"><div class="article-figure-table" id="F2"><div class="article-figure-table-card" id="FIGURE-F2" data-type="F" data-afn="63_JKMS_41_38_e335" data-fn="jkms-41-e335-g002_0063JKMS"><div class="card border-0 my-3"><div class="row no-gutters">
563<div class="col-md-4 mx-auto d-flex justify-content-center flex-wrap align-middle"><div class="card-body">
564<a href="#" class="article-figure-table-btn" data-type="F"><img class="align-top" src="/ArticleImage/0063JKMS/jkms-41-e335-g002-m.jpg"></a>
565</div></div>
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567<p class="card-text"><span class="label"><a href="#" class="article-figure-table-btn" data-type="F">Fig. 2</a>
568</span><span class="capture-id"><br><span class="capture-id">Current evidence landscape for FMT across clinical indications, stratified by certainty of evidence. Clinical indications for FMT are arranged into four evidence tiers according to the GRADE certainty of evidence, ranging from established (high certainty) through emerging-effective (moderate) and emerging-inconsistent (low) to exploratory/insufficient (very low). The color gradient and the horizontal axis both encode decreasing certainty of evidence. Because certainty was graded at the level of individual outcomes, a single indication may occupy more than one tier depending on the outcome considered. Recurrent <i>Clostridioides difficile</i> infection represents the only established indication, supported by multiple randomized controlled trials and meta-analyses as well as regulatory-approved standardized microbiota products. Among inflammatory bowel diseases, FMT for induction of remission in ulcerative colitis shows the strongest non-<i>Clostridioides difficile</i> infection evidence, whereas maintenance of remission is less consistent, and evidence in Crohn’s disease remains exploratory. In irritable bowel syndrome, short
568-term symptom response is supported by low-certainty evidence, but durable response (≥ 12 months) is not established. Metabolic disorders represent an emerging application: lean-donor FMT improves insulin sensitivity, although this effect appears transient and consistent improvement in clinical outcomes such as body weight has not been demonstrated. Neurological disorders remain investigational: in Parkinson's disease, a phase II trial reported motor improvement sustained at 12 months, but a subsequent trials have yielded inconsistent motor outcomes. Evidence for other neurological disorders is limited to a single terminated trial in amyotrophic lateral sclerosis and a safety/feasibility pilot in multiple sclerosis.</span><br><span class="capture-id">FMT = fecal microbiota transplantation.</span></span></p>
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574</div></div></div></div></div></p>
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577<div>
578<div><div class="article-section-header">
579<div class="__SECTION__" id="__ID_SECTION_4" data-section-name="MECHANISTIC RATIONALE FOR FMT"><div class="dropdown">
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581</div></div>
582<h2>MECHANISTIC RATIONALE FOR FMT</h2>
583</div></div>
584<p>Three cross-cutting mechanistic themes support the rationale for expanding FMT: i) metabolite signaling axes (including SCFAs, bile acids, tryptophan-derived metabolites) that influence host metabolism, immunity, and neuroinflammation, ii) barrier and immune axes, whereby microbiome restoration reinforces epithelial integrity and supports regulatory immune pathways, and iii) gut–brain axes that enable bidirectional communication through neural, immune, and endocrine routes.<span class="xref"><span id="XREF_B24" class="ref-destination-back"></span><a href="#B24" data-id="XREF_B24" data-toggle="ref-popover" data-trigger="manual" data-placement="right">24</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B26" class="ref-destination-back"></span><a href="#B26" data-id="XREF_B26" data-toggle="ref-popover" data-trigger="manual" data-placement="right">26</a></span></p>
585<div>
586<p class="article-section-sub-title article-section-sub-title-level-2"><h3>Colonization resistance and competitive exclusion</h3></p>
587<p>CDI is an archetypal dysbiosis-driven condition in which antibiotic disruption reduces colonization resistance, allowing <i>C. difficile</i> to proliferate and produce toxins. FMT exerts its therapeutic effects through several interconnected mechanisms: restoration of microbial diversity and function; competitive exclusion of pathogenic bacteria and enhancement of colonization resistance; production of antimicrobial and trophic metabolites such as SCFAs; modulation of bile acid metabolism; and improvement of gut barrier integrity and immune homeostasis.<span class="xref"><span id="XREF_B15" class="ref-destination-back"></span><a href="#B15" data-id="XREF_B15" data-toggle="ref-popover" data-trigger="manual" data-placement="right">15</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B27" class="ref-destination-back"></span><a href="#B27" data-id="XREF_B27" data-toggle="ref-popover" data-trigger="manual" data-placement="right">27</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B28" class="ref-destination-back"></span><a href="#B28" data-id="XREF_B28" data-toggle="ref-popover" data-trigger="manual" data-placement="right">28</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B29" class="ref-destination-back"></span><a href="#B29" data-id="XREF_B29" data-toggle="ref-popover" data-trigger="manual" data-placement="right">29</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B30" class="ref-destination-back"></span><a href="#B30" data-id="XREF_B30" data-toggle="ref-popover" data-trigger="manual" data-placement="right">30</a></span> These mechanisms provide a biological basis for FMT beyond CDI, particularly when dysbiosis contributes to metabolic or neuroimmune dysfunction.</p>
588</div>
589<div>
590<p class="article-section-sub-title article-section-sub-title-level-2"><h3>Metabolite signaling axes and immune modulation</h3></p>
591<p>The gut microbiota influences host energy metabolism through the fermentation of dietary fibers and the production of SCFAs, which serve as key mediators that affect enteroendocrine signaling, appetite regulation, insulin sensitivity, and lipid metabolism.<span class="xref"><span id="XREF_B31" class="ref-destination-back"></span><a href="#B31" data-id="XREF_B31" data-toggle="ref-popover" data-trigger="manual" data-placement="right">31</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B32" class="ref-destination-back"></span><a href="#B32" data-id="XREF_B32" data-toggle="ref-popover" data-trigger="manual" data-placement="right">32</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B33" class="ref-destination-back"></span><a href="#B33" data-id="XREF_B33" data-toggle="ref-popover" data-trigger="manual" data-placement="right">33</a></span> Butyrate, for example, serves as an energy source for colonocytes and modulates immune cell activity, promoting regulatory T cell differentiation and suppressing pro-inflammatory cytokine production.<span class="xref"><span id="XREF_B26" class="ref-destination-back"></span><a href="#B26" data-id="XREF_B26" data-toggle="ref-popover" data-trigger="manual" data-placement="right">26</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B28" class="ref-destination-back"></span><a href="#B28" data-id="XREF_B28" data-toggle="ref-popover" data-trigger="manual" data-placement="right">28</a></span> Increased SCFA availability after microbiome restoration may improve insulin sensitivity and reduce inflammatory cytokine signaling.<span class="xref"><span id="XREF_B32" class="ref-destination-back"></span><a href="#B32" data-id="XREF_B32" data-toggle="ref-popover" data-trigger="manual" data-placement="right">32</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B33" class="ref-destination-back"></span><a href="#B33" data-id="XREF_B33" data-toggle="ref-popover" data-trigger="manual" data-placement="right">33</a></span> Bile acid transformation by microbiota reshapes the bile acid pool and signaling via receptors, such as Farnesoid X receptor and G-protein-coupled bile acid receptor, with downstream effects on lipid metabolism, energy expenditure, and immune regulation.<span class="xref"><span id="XREF_B34" class="ref-destination-back"></span><a href="#B34" data-id="XREF_B34" data-toggle="ref-popover" data-trigger="manual" data-placement="right">34</a></span></p>
592<p>A recurring mechanistic theme across metabolic and neuroinflammatory disorders is impaired gut barrier integrity, leading to increased translocation of microbial products and promoting low-grade systemic inflammation. The healthy gut microbiota contributes to the maintenance of the intestinal barrier by promoting the production of mucus and tight junction proteins. This barrier prevents the translocation of pathogens and antigens into the bloodstream, thereby reducing systemic inflammation and immune activation.<span class="xref"><span id="XREF_B33" class="ref-destination-back"></span><a href="#B33" data-id="XREF_B33" data-toggle="ref-popover" data-trigger="manual" data-placement="right">33</a></span> FMT may improve host phenotypes by introducing beneficial taxa, restoring barrier-associated functions, and lowering inflammation.<span class="xref"><span id="XREF_B29" class="ref-destination-back"></span><a href="#B29" data-id="XREF_B29" data-toggle="ref-popover" data-trigger="manual" data-placement="right">29</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B35" class="ref-destination-back"></span><a href="#B35" data-id="XREF_B35" data-toggle="ref-popover" data-trigger="manual" data-placement="right">35</a></span> As a mechanistic illustration, controlled trials of non-alcoholic fatty liver disease (NAFLD) have reported changes in intestinal permeability, even when liver fat or insulin resistance endpoints do not improve, suggesting that barrier restoration may precede broader metabolic benefits.<span class="xref"><span id="XREF_B36" class="ref-destination-back"></span><a href="#B36" data-id="XREF_B36" data-toggle="ref-popover" data-trigger="manual" data-placement="right">36</a></span></p>
593</div>
594<div>
595<p class="article-section-sub-title article-section-sub-title-level-2"><h3>Gut<b>–</b>brain axis</h3></p>
596<p>The gut–brain axis provides biological plausibility for FMT in neurological disorders through neural pathways (the vagus and enteric nervous systems), immune pathways (systemic cytokines and peripheral immune activation), and microbial metabolites that influence neuroinflammation.<span class="xref"><span id="XREF_B9" class="ref-destination-back"></span><a href="#B9" data-id="XREF_B9" data-toggle="ref-popover" data-trigger="manual" data-placement="right">9</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B37" class="ref-destination-back"></span><a href="#B37" data-id="XREF_B37" data-toggle="ref-popover" data-trigger="manual" data-placement="right">37</a></span> In Parkinson’s disease (PD), the gut-first hypothesis proposes that alpha-synuclein pathology begins in the gut and propagates centrally.<span class="xref"><span id="XREF_B38" class="ref-destination-back"></span><a href="#B38" data-id="XREF_B38" data-toggle="ref-popover" data-trigger="manual" data-placement="right">
59638</a></span> FMT may indirectly reduce neuroinflammation by improving barrier integrity and reducing gut-derived inflammatory signaling, while reshaping metabolite profiles that modulate microglial activation.</p>
597<p>In autoimmune neuroinflammation, microbiome-derived metabolites and microbial signals can shape T cell polarization and peripheral immune responses, ultimately affecting central nervous system inflammation. A recent comprehensive review highlighted gut microbiota-immune interactions as plausible therapeutic targets in multiple sclerosis (MS), motivating microbiome-modifying interventions including FMT and defined microbial consortia.<span class="xref"><span id="XREF_B39" class="ref-destination-back"></span><a href="#B39" data-id="XREF_B39" data-toggle="ref-popover" data-trigger="manual" data-placement="right">39</a></span> In MS, FMT could hypothetically shift the immune balance toward tolerance by expanding regulatory T cells,<span class="xref"><span id="XREF_B40" class="ref-destination-back"></span><a href="#B40" data-id="XREF_B40" data-toggle="ref-popover" data-trigger="manual" data-placement="right">40</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B41" class="ref-destination-back"></span><a href="#B41" data-id="XREF_B41" data-toggle="ref-popover" data-trigger="manual" data-placement="right">41</a></span> restraining pro-inflammatory Th17 responses implicated in demyelination,<span class="xref"><span id="XREF_B42" class="ref-destination-back"></span><a href="#B42" data-id="XREF_B42" data-toggle="ref-popover" data-trigger="manual" data-placement="right">42</a></span> and modulating gut-associated lymphoid tissue, potentially affecting central nervous system inflammation and demyelination.</p>
598</div>
599</div>
600
601<div>
602<div><div class="article-section-header">
603<div class="__SECTION__" id="__ID_SECTION_5" data-section-name="CLINICAL APPLICATION OF FMT"><div class="dropdown">
604<a href="#" class="dropdown-goto dropdown-toggle d-none" id="dropdownGoto_5" title="Go to other sections in this page" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">Go to:</a><div class="dropdown-menu dropdown-menu-right d-none" aria-labelledby="dropdownGoto_5"></div>
605</div></div>
606<h2>CLINICAL APPLICATION OF FMT</h2>
607</div></div>
608<div>
609<p class="article-section-sub-title article-section-sub-title-level-2"><h3>Established indication: rCDI</h3></p>
610<p>FMT has demonstrated a high efficacy for rCDI, particularly in patients with multiple relapses.<span class="xref"><span id="XREF_B43" class="ref-destination-back"></span><a href="#B43" data-id="XREF_B43" data-toggle="ref-popover" data-trigger="manual" data-placement="right">43</a></span> Compared with medical therapy alone, FMT has demonstrated greater eff
610icacy in rCDI than in primary CDI.<span class="xref"><span id="XREF_B44" class="ref-destination-back"></span><a href="#B44" data-id="XREF_B44" data-toggle="ref-popover" data-trigger="manual" data-placement="right">44</a></span> By delivery route, colonoscopy to the lower GI tract achieved the highest cure rate.<span class="xref"><span id="XREF_B45" class="ref-destination-back"></span><a href="#B45" data-id="XREF_B45" data-toggle="ref-popover" data-trigger="manual" data-placement="right">45</a></span> A phase III, double-blind, randomized, placebo-controlled trial of SER-109 in patients with rCDI showed a reduced risk of recurrence over 8 weeks.<span class="xref"><span id="XREF_B46" class="ref-destination-back"></span><a href="#B46" data-id="XREF_B46" data-toggle="ref-popover" data-trigger="manual" data-placement="right">46</a></span> Another phase III, double-blind, randomized, placebo-controlled trial of RBX2660 demonstrated higher treatment success than placebo in rCDI.<span class="xref"><span id="XREF_B47" class="ref-destination-back"></span><a href="#B47" data-id="XREF_B47" data-toggle="ref-popover" data-trigger="manual" data-placement="right">47</a></span> The CDI experience indicates that ecosystem-level interventions can produce robust clinical outcomes. The key question for emerging indications is whether similarly meaningful benefits can be achieved in more complex, multi-faceted diseases, and how to optimize durability and patient stratification.</p>
611</div>
612<div>
613<p class="article-section-sub-title article-section-sub-title-level-2"><h3>GI disorders beyond CDI: IBD and IBS</h3></p>
614<p>IBD includes UC and CD and is characterized by chronic and relapsing intestinal inflammation. IBD pathogenesis is associated with several factors, including genetic susceptibility, immune dysregulation, and environmental factors. Alterations in the intestinal microbiota have also been reported, suggesting a role for microbiota-modulating therapies.<span class="xref"><span id="XREF_B48" class="ref-destination-back"></span><a href="#B48" data-id="XREF_B48" data-toggle="ref-popover" data-trigger="manual" data-placement="right">48</a></span> However, the therapeutic application of FMT in IBD is still in the early stages of development.<span class="xref"><span id="XREF_B49" class="ref-destination-back"></span><a href="#B49" data-id="XREF_B49" data-toggle="ref-popover" data-trigger="manual" data-placement="right">49</a></span> RCTs in UC have shown conflicting results (<span class="fig-table-link"><a href="#T1">Table 1</a></span>).<span class="xref"><span id="XREF_B50" class="ref-destination-back"></span><a href="#B50" data-id="XREF_B50" data-toggle="ref-popover" data-trigger="manual" data-placement="right">50</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B51" class="ref-destination-back"></span><a href="#B51" data-id="XREF_B51" data-toggle="ref-popover" data-trigger="manual" data-placement="right">51</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B52" class="ref-destination-back"></span><a href="#B52" data-id="XREF_B52" data-toggle="ref-popover" data-trigger="manual" data-placement="right">52</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B53" class="ref-destination-back"></span><a href="#B53" data-id="XREF_B53" data-toggle="ref-popover" data-trigger="manual" data-placement="right">53</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B54" class="ref-destination-back"></span><a href="#B54" data-id="XREF_B54" data-toggle="ref-popover" data-trigger="manual" data-placement="right">54</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B55" class="ref-destination-back"></span><a href="#B55" data-id="XREF_B55" data-toggle="ref-popover" data-trigger="manual" data-placement="right">55</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B56" class="ref-destination-back"></span><a href="#B56" data-id="XREF_B56" data-toggle="ref-popover" data-trigger="manual" data-placement="right">56</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B57" class="ref-destination-back"></span><a href="#B57" data-id="XREF_B57" data-toggle="ref-popover" data-trigger="manual" data-placement="right">57</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B58" class="ref-destination-back"></span><a href="#B58" data-id="XREF_B58" data-toggle="ref-popover" data-trigger="manual" data-placement="right">58</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B59" class="ref-destination-back"></span><a href="#B59" data-id="XREF_B59" data-toggle="ref-popover" data-trigger="manual" data-placement="right">59</a></span> Across ten controlled trials of FMT in UC, FMT has induced remission in UC most consistently when delivered intensively through multidonor pooling, repeated dosing, or antibiotic pre-conditioning, implying a donor effect and a possible dose–response relationship.<span class="xref"><span id="XREF_B52" class="ref-destination-back"></span><a href="#B52" data-id="XREF_B52" data-toggle="ref-popover" data-trigger="manual" data-placement="right">52</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B53" class="ref-destination-back"></span><a href="#B53" data-id="XREF_B53" data-toggle="ref-popover" data-trigger="manual" data-placement="right">53</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B58" class="ref-destination-back"></span><a href="#B58" data-id="XREF_B58" data-toggle="ref-popover" data-trigger="manual" data-placement="right">58</a></span> Reported efficacy is further modulated by route of administration, the intensity and duration of dosing, and the use or absence of maintenance therapy, none of which has been standardized. FMT has not entered routine clinical practice for UC because the evidence base is heterogeneous and of limited long-term durability, and effective, well-characterized immunomodulatory medications and biological agents remain the mainstay of therapy.<span class="xref"><span id="XREF_B62" class="ref-destination-back"></span><a href="#B62" data-id="XREF_B62" data-toggle="ref-popover" data-trigger="manual" data-placement="right">62</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B63" class="ref-destination-back"></span><a href="#B63" data-id="XREF_B63" data-toggle="ref-popover" data-trigger="manual" data-placement="right">63</a></span> The evidence for CD is far less well established, limited to small trials and pilot maintenance studies (<span class="fig-table-link"><a href="#T1">Table 1</a></span>
614).<span class="xref"><span id="XREF_B60" class="ref-destination-back"></span><a href="#B60" data-id="XREF_B60" data-toggle="ref-popover" data-trigger="manual" data-placement="right">60</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B61" class="ref-destination-back"></span><a href="#B61" data-id="XREF_B61" data-toggle="ref-popover" data-trigger="manual" data-placement="right">61</a></span> A recent umbrella review reported pooled estimates of a 47.5% final remission rate and a 71.7% clinical response rate after FMT in CD; these figures, however, were derived from single-arm pooling of cohort and non-randomized studies that also included pediatric patients, and were rated as moderate and very low certainty, respectively.<span class="xref"><span id="XREF_B43" class="ref-destination-back"></span><a href="#B43" data-id="XREF_B43" data-toggle="ref-popover" data-trigger="manual" data-placement="right">43</a></span> In controlled comparisons the effect is considerably more modest, and further research is necessary to determine the optimal protocols and long-term outcomes.<div class="image-at-section"></div><div class="image-at-section"></div></p>
615<p><div class="article-table image-at-section"><div class="article-figure-table" id="T1"><div class="article-figure-table-card" id="TABLE-T1" data-type="T" data-afn="63_JKMS_41_38_e335" data-fn="jkms-41-e335-i001_0063JKMS"><div class="card border-0 my-3"><div class="row no-gutters">
616<div class="col-md-4 mx-auto d-flex justify-content-center flex-wrap align-middle"><div class="card-body">
617<a href="#" class="article-figure-table-btn" data-type="TH"><img class="align-top" src="/ArticleImage/0063JKMS/jkms-41-e335-i001-m.jpg"></a>
618</div></div>
619<div class="col-md-8"><div class="card-body">
620<p class="card-text"><span class="label"><a href="#" class="article-figure-table-btn" data-type="T">Table 1</a>
621</span><span class="capture-id"><br><span class="capture-id">RCTs of FMT in inflammatory bowel disease</span></span></p>
622<ul class="list-inline">
623<li class="list-inline-item"><a role="button" class="btn btn-outline-article btn-sm article-figure-table-btn" data-type="T">Click for larger image</a></li>
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625<li class="list-inline-item"><a role="button" class="btn btn-outline-article btn-sm" href="ViewImagePopup.php?Type=TX&amp;id=T1&amp;afn=63_JKMS_41_38_e335&amp;fn=jkms-41-e335-i001_0063JKMS" target="_blank">Download as Excel file</a></li>
626</ul>
627</div></div>
628</div></div></div></div></div></p>
629<p>IBS is characterized by alterations in stool frequency and consistency, as well as abdominal discomfort or pain. The pathophysiology of IBS is multifactorial and includes intestinal dysmotility, visceral hypersensitivity, and disordered gut–brain interactions.<span class="xref"><span id="XREF_B5" class="ref-destination-back"></span><a href="#B5" data-id="XREF_B5" data-toggle="ref-popover" data-trigger="manual" data-placement="right">5</a></span> However, the efficacy of FMT in IBS remains unclear (<span class="fig-table-link"><a href="#T2">Table 2</a></span>).<span class="xref"><span id="XREF_B64" class="ref-destination-back"></span><a href="#B64" data-id="XREF_B64" data-toggle="ref-popover" data-trigger="manual" data-placement="right">64</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B65" class="ref-destination-back"></span><a href="#B65" data-id="XREF_B65" data-toggle="ref-popover" data-trigger="manual" data-placement="right">65</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B66" class="ref-destination-back"></span><a href="#B66" data-id="XREF_B66" data-toggle="ref-popover" data-trigger="manual" data-placement="right">66</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B67" class="ref-destination-back"></span><a href="#B67" data-id="XREF_B67" data-toggle="ref-popover" data-trigger="manual" data-placement="right">67</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B68" class="ref-destination-back"></span><a href="#B68" data-id="XREF_B68" data-toggle="ref-popover" data-trigger="manual" data-placement="right">68</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B69" class="ref-destination-back"></span><a href="#B69" data-id="XREF_B69" data-toggle="ref-popover" data-trigger="manual" data-placement="right">69</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B70" class="ref-destination-back"></span><a href="#B70" data-id="XREF_B70" data-toggle="ref-popover" data-trigger="manual" data-placement="right">70</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B71" class="ref-destination-back"></span><a href="#B71" data-id="XREF_B71" data-toggle="ref-popover" data-trigger="manual" data-placement="right">71</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B72" class="ref-destination-back"></span><a href="#B72" data-id="XREF_B72" data-toggle="ref-popover" data-trigger="manual" data-placement="right">72</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B73" class="ref-destination-back"></span><a href="#B73" data-id="XREF_B73" data-toggle="ref-popover" data-trigger="manual" data-placement="right">73</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B74" class="ref-destination-back"></span><a href="#B74" data-id="XREF_B74" data-toggle="ref-popover" data-trigger="manual" data-placement="right">74</a></span> Some studies have reported symptom improvement, particularly in diarrhea-predominant IBS,<span class="xref"><span id="XREF_B64" class="ref-destination-back"></span><a href="#B64" data-id="XREF_B64" data-toggle="ref-popover" data-trigger="manual" data-placement="right">64</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B68" class="ref-destination-back"></span><a href="#B68" data-id="XREF_B68" data-toggle="ref-popover" data-trigger="manual" data-placement="right">68</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B70" class="ref-destination-back"></span><a href="#B70" data-id="XREF_B70" data-toggle="ref-popover" data-trigger="manual" data-placement="right">70</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B73" class="ref-destination-back"></span><a href="#B73" data-id="XREF_B73" data-toggle="ref-popover" data-trigger="manual" data-placement="right">73</a></span> whereas others have shown limited benefits.<span class="xref"><span id="XREF_B65" class="ref-destination-back"></span><a href="#B65" data-id="XREF_B65" data-toggle="ref-popover" data-trigger="manual" data-placement="right">65</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B66" class="ref-destination-back"></span><a href="#B66" data-id="XREF_B66" data-toggle="ref-popover" data-trigger="manual" data-placement="right">66</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B67" class="ref-destination-back"></span><a href="#B67" data-id="XREF_B67" data-toggle="ref-popover" data-trigger="manual" data-placement="right">67</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B69" class="ref-destination-back"></span><a href="#B69" data-id="XREF_B69" data-toggle="ref-popover" data-trigger="manual" data-placement="right">69</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B71" class="ref-destination-back"></span><a href="#B71" data-id="XREF_B71" data-toggle="ref-popover" data-trigger="manual" data-placement="right">71</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B72" class="ref-destination-back"></span><a href="#B72" data-id="XREF_B72" data-toggle="ref-popover" data-trigger="manual" data-placement="right">72</a></span> More recent double-blind trials reinforce this inconsistency. Duodenal FMT failed to meet its primary symptom endpoint despite improving bloating,<span class="xref"><span id="XREF_B72" class="ref-destination-back"></span><a href="#B72" data-id="XREF_B72" data-toggle="ref-popover" data-trigger="manual" data-placement="right">72</a></span> whereas single colonoscopic and capsule-based protocols were largely ineffective.<span class="xref"><span id="XREF_B66" class="ref-destination-back"></span><a href="#B66" data-id="XREF_B66" data-toggle="ref-popover" data-trigger="manual" data-placement="right">66</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B71" class="ref-destination-back"></span><a href="#B71" data-id="XREF_B71" data-toggle="ref-popover" data-trigger="manual" data-placement="right">71</a></span> A more recent double-blind, placebo-controlled trial, however, found that both capsule and enema FMT from a single donor produced significantly higher symptom response rates than placebo (86.7% and 73.3% vs. 26.7%, respectively), with benefit sustained at 12 weeks, suggesting that rigorous donor selection may be more decisive than the route of administration.<span class="xref"><span id="XREF_B74" class="ref-destination-back"></span><a href="#B74" data-id="XREF_B74" data-toggle="ref-popover" data-trigger="manual" data-placement="right">74</a></span> Given the heterogeneous designs, follow-up durations, and outcome measures across these trials, further studies should examine patient selection, route of administration, donor type, infusion frequency, and long-term use.<span class="xref"><span id="XREF_B75" class="ref-destination-back"></span><a href="#B75" data-id="XREF_B75" data-toggle="ref-popover" data-trigger="manual" data-placement="right">75</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B76" class="ref-destination-back"></span><a href="#B76" data-id="XREF_B76" data-toggle="ref-popover" data-trigger="manual" data-placement="right">76</a></span><div class="image-at-section"></div></p>
630<p><div class="article-table image-at-section"><div class="article-figure-table" id="T2"><div class="article-figure-table-card" id="TABLE-T2" data-type="T" data-afn="63_JKMS_41_38_e335" data-fn="jkms-41-e335-i002_0063JKMS"><div class="card border-0 my-3"><div class="row no-gutters">
631<div class="col-md-4 mx-auto d-flex justify-content-center flex-wrap align-middle"><div class="card-body">
632<a href="#" class="article-figure-table-btn" data-type="TH"><img class="align-top" src="/ArticleImage/0063JKMS/jkms-41-e335-i002-m.jpg"></a>
633</div></div>
634<div class="col-md-8"><div class="card-body">
635<p class="card-text"><span class="label"><a href="#" class="article-figure-table-btn" data-type="T">Table 2</a>
636</span><span class="capture-id"><br><span class="capture-id">
636RCTs of FMT in irritable bowel syndrome</span></span></p>
637<ul class="list-inline">
638<li class="list-inline-item"><a role="button" class="btn btn-outline-article btn-sm article-figure-table-btn" data-type="T">Click for larger image</a></li>
639<li class="list-inline-item"><a role="button" class="btn btn-outline-article btn-sm article-figure-table-btn" data-type="TH">Click for full table</a></li>
640<li class="list-inline-item"><a role="button" class="btn btn-outline-article btn-sm" href="ViewImagePopup.php?Type=TX&amp;id=T2&amp;afn=63_JKMS_41_38_e335&amp;fn=jkms-41-e335-i002_0063JKMS" target="_blank">Download as Excel file</a></li>
641</ul>
642</div></div>
643</div></div></div></div></div></p>
644</div>
645<div>
646<p class="article-section-sub-title article-section-sub-title-level-2"><h3>Metabolic disorders</h3></p>
647<p>Emerging research suggests potential benefits of FMT in metabolic disorders, including insulin resistance, obesity, and NAFLD (<span class="fig-table-link"><a href="#T3">Table 3</a></span>).<span class="xref"><span id="XREF_B36" class="ref-destination-back"></span><a href="#B36" data-id="XREF_B36" data-toggle="ref-popover" data-trigger="manual" data-placement="right">36</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B77" class="ref-destination-back"></span><a href="#B77" data-id="XREF_B77" data-toggle="ref-popover" data-trigger="manual" data-placement="right">77</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B78" class="ref-destination-back"></span><a href="#B78" data-id="XREF_B78" data-toggle="ref-popover" data-trigger="manual" data-placement="right">78</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B79" class="ref-destination-back"></span><a href="#B79" data-id="XREF_B79" data-toggle="ref-popover" data-trigger="manual" data-placement="right">79</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B80" class="ref-destination-back"></span><a href="#B80" data-id="XREF_B80" data-toggle="ref-popover" data-trigger="manual" data-placement="right">80</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B81" class="ref-destination-back"></span><a href="#B81" data-id="XREF_B81" data-toggle="ref-popover" data-trigger="manual" data-placement="right">81</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B82" class="ref-destination-back"></span><a href="#B82" data-id="XREF_B82" data-toggle="ref-popover" data-trigger="manual" data-placement="right">82</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B83" class="ref-destination-back"></span><a href="#B83" data-id="XREF_B83" data-toggle="ref-popover" data-trigger="manual" data-placement="right">83</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B84" class="ref-destination-back"></span><a href="#B84" data-id="XREF_B84" data-toggle="ref-popover" data-trigger="manual" data-placement="right">84</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B85" class="ref-destination-back"></span><a href="#B85" data-id="XREF_B85" data-toggle="ref-popover" data-trigger="manual" data-placement="right">85</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B86" class="ref-destination-back"></span><a href="#B86" data-id="XREF_B86" data-toggle="ref-popover" data-trigger="manual" data-placement="right">86</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B87" class="ref-destination-back"></span><a href="#B87" data-id="XREF_B87" data-toggle="ref-popover" data-trigger="manual" data-placement="right">87</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B88" class="ref-destination-back"></span><a href="#B88" data-id="XREF_B88" data-toggle="ref-popover" data-trigger="manual" data-placement="right">88</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B89" class="ref-destination-back"></span><a href="#B89" data-id="XREF_B89" data-toggle="ref-popover" data-trigger="manual" data-placement="right">89</a></span> A landmark study reported improved peripheral insulin sensitivity 6 weeks after lean-donor FMT in male patients with metabolic 
647syndrome.<span class="xref"><span id="XREF_B77" class="ref-destination-back"></span><a href="#B77" data-id="XREF_B77" data-toggle="ref-popover" data-trigger="manual" data-placement="right">77</a></span> Another RCT in male patients with metabolic syndrome also demonstrated that lean-donor FMT can transiently improve insulin sensitivity and that baseline recipient microbiome features may predict the metabolic response.<span class="xref"><span id="XREF_B78" class="ref-destination-back"></span><a href="#B78" data-id="XREF_B78" data-toggle="ref-popover" data-trigger="manual" data-placement="right">78</a></span> A phase II RCT of single-dose oral FMT demonstrated that combining FMT with low-fermentable fiber supplementation resulted in a sustained 27.6% improvement in insulin sensitivity at 6 weeks, compared with no significant effect with high-fermentable fiber.<span class="xref"><span id="XREF_B82" class="ref-destination-back"></span><a href="#B82" data-id="XREF_B82" data-toggle="ref-popover" data-trigger="manual" data-placement="right">82</a></span> Subsequent meta-analyses have supported improvements in lipid profiles and insulin sensitivity markers (e.g., Homeostatic Model Assessment for Insulin Resistance score) following FMT, although weight loss has not been consistently observed.<span class="xref"><span id="XREF_B90" class="ref-destination-back"></span><a href="#B90" data-id="XREF_B90" data-toggle="ref-popover" data-trigger="manual" data-placement="right">90</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B91" class="ref-destination-back"></span><a href="#B91" data-id="XREF_B91" data-toggle="ref-popover" data-trigger="manual" data-placement="right">91</a></span> This pattern supports the concept that FMT improves metabolic function primarily through metabolite signaling and modulation of inflammatory pathways rather than through immediate changes in adiposity.<span class="xref"><span id="XREF_B33" class="ref-destination-back"></span><a href="#B33" data-id="XREF_B33" data-toggle="ref-popover" data-trigger="manual" data-placement="right">33</a></span><div class="image-at-section"></div></p>
648<p><div class="article-table image-at-section"><div class="article-figure-table" id="T3"><div class="article-figure-table-card" id="TABLE-T3" data-type="T" data-afn="63_JKMS_41_38_e335" data-fn="jkms-41-e335-i003_0063JKMS"><div class="card border-0 my-3"><div class="row no-gutters">
649<div class="col-md-4 mx-auto d-flex justify-content-center flex-wrap align-middle"><div class="card-body">
650<a href="#" class="article-figure-table-btn" data-type="TH"><img class="align-top" src="/ArticleImage/0063JKMS/jkms-41-e335-i003-m.jpg"></a>
651</div></div>
652<div class="col-md-8"><div class="card-body">
653<p class="card-text"><span class="label"><a href="#" class="article-figure-table-btn" data-type="T">Table 3</a>
654</span><span class="capture-id"><br><span class="capture-id">RCTs of FMT in metabolic disorders</span></span></p>
655<ul class="list-inline">
656<li class="list-inline-item"><a role="button" class="btn btn-outline-article btn-sm article-figure-table-btn" data-type="T">Click for larger image</a></li>
657<li class="list-inline-item"><a role="button" class="btn btn-outline-article btn-sm article-figure-table-btn" data-type="TH">Click for full table</a></li>
658<li class="list-inline-item"><a role="button" class="btn btn-outline-article btn-sm" href="ViewImagePopup.php?Type=TX&amp;id=T3&amp;afn=63_JKMS_41_38_e335&amp;fn=jkms-41-e335-i003_0063JKMS" target="_blank">Download as Excel file</a></li>
659</ul>
660</div></div>
661</div></div></div></div></div></p>
662<p>Trials on metabolic syndrome suggest that FMT can alter recipient microbiota composition; however, consistent and durable improvements in clinical endpoints have not been demonstrated, likely reflecting the host, diet, and behavioral determinants of metabolic adaptation.<span class="xref"><span id="XREF_B78" class="ref-destination-back"></span><a href="#B78" data-id="XREF_B78" data-toggle="ref-popover" data-trigger="manual" data-placement="right">78</a></span> Most trials demonstrate transient biological improvements rather than sustained clinical benefit, while durable reductions in body weight, glycemic control, or hepatic steatosis remain inconsistent.<span class="xref"><span id="XREF_B77" class="ref-destination-back"></span><a href="#B77" data-id="XREF_B77" data-toggle="ref-popover" data-trigger="manual" data-placement="right">77</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B78" class="ref-destination-back"></span><a href="#B78" data-id="XREF_B78" data-toggle="ref-popover" data-trigger="manual" data-placement="right">78</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B82" class="ref-destination-back"></span><a href="#B82" data-id="XREF_B82" data-toggle="ref-popover" data-trigger="manual" data-placement="right">82</a></span> Consistent with this pattern, a recent sham-controlled pilot trial in metabolic 
662syndrome found that a single FMT improved insulin resistance at 6 weeks, but the effect was no longer significant by 12 weeks.<span class="xref"><span id="XREF_B89" class="ref-destination-back"></span><a href="#B89" data-id="XREF_B89" data-toggle="ref-popover" data-trigger="manual" data-placement="right">89</a></span> Current evidence therefore suggests that microbial manipulation alone is unlikely to be sufficient, and that combining FMT with appropriate dietary interventions and identifying predictors of engraftment success may be crucial for optimizing outcomes.</p>
663<p>Several studies have indicated that the gut microbiota plays a role in the management of type 2 diabetes mellitus (T2DM).<span class="xref"><span id="XREF_B92" class="ref-destination-back"></span><a href="#B92" data-id="XREF_B92" data-toggle="ref-popover" data-trigger="manual" data-placement="right">92</a></span> However, evidence for the clinical application of FMT in T2DM remains limited.<span class="xref"><span id="XREF_B80" class="ref-destination-back"></span><a href="#B80" data-id="XREF_B80" data-toggle="ref-popover" data-trigger="manual" data-placement="right">80</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B81" class="ref-destination-back"></span><a href="#B81" data-id="XREF_B81" data-toggle="ref-popover" data-trigger="manual" data-placement="right">81</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B93" class="ref-destination-back"></span><a href="#B93" data-id="XREF_B93" data-toggle="ref-popover" data-trigger="manual" data-placement="right">93</a></span> An RCT on newly diagnosed patients with T2DM reported improvements in insulin resistance metrics and body mass index after FMT (alone or combined with metformin), suggesting potential metabolic benefits in selected contexts.<span class="xref"><span id="XREF_B86" class="ref-destination-back"></span><a href="#B86" data-id="XREF_B86" data-toggle="ref-popover" data-trigger="manual" data-placement="right">86</a></span> However, the results remain inconsistent across studies, and optimal patient selection criteria, donor characteristics, and treatment protocols have yet to be established.<span class="xref"><span id="XREF_B84" class="ref-destination-back"></span><a href="#B84" data-id="XREF_B84" data-toggle="ref-popover" data-trigger="manual" data-placement="right">84</a></span> Evidence in type 1 diabetes is even more preliminary; an exploratory double-blind RCT unexpectedly found that autologous FMT preserved residual beta-cell function (stimulated C-peptide) better than allogenic FMT at 12 months,<span class="xref"><span id="XREF_B83" class="ref-destination-back"></span><a href="#B83" data-id="XREF_B83" data-toggle="ref-popover" data-trigger="manual" data-placement="right">83</a></span> reinforcing that donor selection and host context can shape the direction of the metabolic response.</p>
664<p>NAFLD represents another promising target given the gut-liver axis and the role of microbial metabolites in hepatic inflammation and fibrosis.<span class="xref"><span id="XREF_B87" class="ref-destination-back"></span><a href="#B87" data-id="XREF_B87" data-toggle="ref-popover" data-trigger="manual" data-placement="right">87</a></span> Clinical evidence for FMT in NAFLD shows mixed results depending on endpoints, route, dosing, and population.<span class="xref"><span id="XREF_B36" class="ref-destination-back"></span><a href="#B36" data-id="XREF_B36" data-toggle="ref-popover" data-trigger="manual" data-placement="right">36</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B87" class="ref-destination-back"></span><a href="#B87" data-id="XREF_B87" data-toggle="ref-popover" data-trigger="manual" data-placement="right">87</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B88" class="ref-destination-back"></span><a href="#B88" data-id="XREF_B88" data-toggle="ref-popover" data-trigger="manual" data-placement="right">88</a></span> Notably, while studies on NAFLD support the concept that FMT can modify barrier integrity and microbiome features, hepatic steatosis and insulin resistance endpoints have not shown consistent improvement.<span class="xref"><span id="XREF_B36" class="ref-destination-back"></span><a href="#B36" data-id="XREF_B36" data-toggle="ref-popover" data-trigger="manual" data-placement="right">36</a></span></p>
665</div>
666<div>
667<p class="article-section-sub-title article-section-sub-title-level-2"><h3>Neurological disorders</h3></p>
668<p>PD has received particular attention because of the gut-first hypothesis and evidence that gut microbiome alterations may precede motor manifestations.<span class="xref"><span id="XREF_B38" class="ref-destination-back"></span><a href="#B38" data-id="XREF_B38" data-toggle="ref-popover" data-trigger="manual" data-placement="right">
66838</a></span> In preclinical models, microbiome manipulation and FMT improved locomotor function and reduced levels of neuroinflammatory markers.<span class="xref"><span id="XREF_B94" class="ref-destination-back"></span><a href="#B94" data-id="XREF_B94" data-toggle="ref-popover" data-trigger="manual" data-placement="right">94</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B95" class="ref-destination-back"></span><a href="#B95" data-id="XREF_B95" data-toggle="ref-popover" data-trigger="manual" data-placement="right">95</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B96" class="ref-destination-back"></span><a href="#B96" data-id="XREF_B96" data-toggle="ref-popover" data-trigger="manual" data-placement="right">96</a></span> Clinical evidence is emerging (<span class="fig-table-link"><a href="#T4">Table 4</a></span>).<span class="xref"><span id="XREF_B97" class="ref-destination-back"></span><a href="#B97" data-id="XREF_B97" data-toggle="ref-popover" data-trigger="manual" data-placement="right">97</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B98" class="ref-destination-back"></span><a href="#B98" data-id="XREF_B98" data-toggle="ref-popover" data-trigger="manual" data-placement="right">98</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B99" class="ref-destination-back"></span><a href="#B99" data-id="XREF_B99" data-toggle="ref-popover" data-trigger="manual" data-placement="right">99</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B100" class="ref-destination-back"></span><a href="#B100" data-id="XREF_B100" data-toggle="ref-popover" data-trigger="manual" data-placement="right">100</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B101" class="ref-destination-back"></span><a href="#B101" data-id="XREF_B101" data-toggle="ref-popover" data-trigger="manual" data-placement="right">101</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B102" class="ref-destination-back"></span><a href="#B102" data-id="XREF_B102" data-toggle="ref-popover" data-trigger="manual" data-placement="right">102</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B103" class="ref-destination-back"></span><a href="#B103" data-id="XREF_B103" data-toggle="ref-popover" data-trigger="manual" data-placement="right">103</a></span> A phase II randomized, double-blind, placebo-controlled trial (GUT-PARFECT) reported mild but potentially long-lasting improvements in motor outcomes, with effects sustained for 12 months.<span class="xref"><span id="XREF_B99" class="ref-destination-back"></span><a href="#B99" data-id="XREF_B99" data-toggle="ref-popover" data-trigger="manual" data-placement="right">99</a></span> Another study reported improvements in constipation and non-motor symptoms after repeat-dose oral FMT in patients with PD and constipation.<span class="xref"><span id="XREF_B98" class="ref-destination-back"></span><a href="#B98" data-id="XREF_B98" data-toggle="ref-popover" data-trigger="manual" data-placement="right">98</a></span> A recent systematic review of clinical trials concluded that FMT appeared to be feasible and generally safe in the studied cohorts, with variable symptom improvements and substantial heterogeneity across protocols and outcome measures.<span class="xref"><span id="XREF_B104" class="ref-destination-back"></span><a href="#B104" data-id="XREF_B104" data-toggle="ref-popover" data-trigger="manual" data-placement="right">104</a></span> However, a subsequent double-blind trial found no motor benefit,<span class="xref"><span id="XREF_B100" class="ref-destination-back"></span><a href="#B100" data-id="XREF_B100" data-toggle="ref-popover" data-trigger="manual" data-placement="right">100</a></span> and the overall certainty of a clinically meaningful motor benefit in PD remains low.<div class="image-at-section"></div></p>
669<p><div class="article-table image-at-section"><div class="article-figure-table" id="T4"><div class="article-figure-table-card" id="TABLE-T4" data-type="T" data-afn="63_JKMS_41_38_e335" data-fn="jkms-41-e335-i004_0063JKMS"><div class="card border-0 my-3"><div class="row no-gutters">
670<div class="col-md-4 mx-auto d-flex justify-content-center flex-wrap align-middle"><div class="card-body">
671<a href="#" class="article-figure-table-btn" data-type="TH"><img class="align-top" src="/ArticleImage/0063JKMS/jkms-41-e335-i004-m.jpg"></a>
672</div></div>
673<div class="col-md-8"><div class="card-body">
674<p class="card-text"><span class="label"><a href="#" class="article-figure-table-btn" data-type="T">Table 4</a>
675</span><span class="capture-id"><br><span class="capture-id">RCTs of FMT in neurological disorders</span></span></p>
676<ul class="list-inline">
677<li class="list-inline-item">
677<a role="button" class="btn btn-outline-article btn-sm article-figure-table-btn" data-type="T">Click for larger image</a></li>
678<li class="list-inline-item"><a role="button" class="btn btn-outline-article btn-sm article-figure-table-btn" data-type="TH">Click for full table</a></li>
679<li class="list-inline-item"><a role="button" class="btn btn-outline-article btn-sm" href="ViewImagePopup.php?Type=TX&amp;id=T4&amp;afn=63_JKMS_41_38_e335&amp;fn=jkms-41-e335-i004_0063JKMS" target="_blank">Download as Excel file</a></li>
680</ul>
681</div></div>
682</div></div></div></div></div></p>
683<p>MS is associated with distinctive alterations in the microbiota.<span class="xref"><span id="XREF_B40" class="ref-destination-back"></span><a href="#B40" data-id="XREF_B40" data-toggle="ref-popover" data-trigger="manual" data-placement="right">40</a></span> Evidence for FMT in MS is limited; however, reported outcomes, such as stabilization of disability or functional improvement, have generated interest.<span class="xref"><span id="XREF_B39" class="ref-destination-back"></span><a href="#B39" data-id="XREF_B39" data-toggle="ref-popover" data-trigger="manual" data-placement="right">39</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B102" class="ref-destination-back"></span><a href="#B102" data-id="XREF_B102" data-toggle="ref-popover" data-trigger="manual" data-placement="right">102</a></span> Mechanistically oriented reviews emphasize that the gut microbiota can modulate systemic immune responses relevant to MS and outline microbiome-targeted therapeutic strategies, while also highlighting the need for well-powered human studies with rigorous phenotyping and longitudinal sampling.<span class="xref"><span id="XREF_B39" class="ref-destination-back"></span><a href="#B39" data-id="XREF_B39" data-toggle="ref-popover" data-trigger="manual" data-placement="right">39</a></span> Given the autoimmune nature of MS, careful patient selection and monitoring for potential immune-mediated adverse events are essential.</p>
684<p>Evidence in other neurodegenerative diseases is weaker still. A double-blind RCT in amyotrophic lateral sclerosis found no improvement in the primary functional endpoint (Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised), with benefit limited to non-motor symptoms.<span class="xref"><span id="XREF_B103" class="ref-destination-back"></span><a href="#B103" data-id="XREF_B103" data-toggle="ref-popover" data-trigger="manual" data-placement="right">103</a></span> The role of microbiota modulation in Alzheimer’s disease has also been proposed; however, clinical evidence remains lacking, and current data are limited to animal models.<span class="xref"><span id="XREF_B105" class="ref-destination-back"></span><a href="#B105" data-id="XREF_B105" data-toggle="ref-popover" data-trigger="manual" data-placement="right">105</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B106" class="ref-destination-back"></span><a href="#B106" data-id="XREF_B106" data-toggle="ref-popover" data-trigger="manual" data-placement="right">106</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B107" class="ref-destination-back"></span><a href="#B107" data-id="XREF_B107" data-toggle="ref-popover" data-trigger="manual" data-placement="right">107</a></span> Although the gut–brain axis provides a compelling biological rationale for FMT in neurological diseases, current clinical evidence remains preliminary. Consequently, these findings should be regarded as hypothesis-generating, and large multicenter randomized trials with long-term follow-up are required before FMT can be recommended for routine neurological practice.</p>
685</div>
686</div>
687
688<div>
689<div><div class="article-section-header">
690<div class="__SECTION__" id="__ID_SECTION_6" data-section-name="SAFETY CONSIDERATIONS"><div class="dropdown">
691<a href="#" class="dropdown-goto dropdown-toggle d-none" id="dropdownGoto_6" title="Go to other sections in this page" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">Go to:</a><div class="dropdown-menu dropdown-menu-right d-none" aria-labelledby="dropdownGoto_6"></div>
692</div></div>
693<h2>SAFETY CONSIDERATIONS</h2>
694</div></div>
695<div>
696<p class="article-section-sub-title article-section-sub-title-level-2"><h3>Adverse event profile</h3></p>
697<p>FMT is generally well-tolerated, with most adverse events being mild to moderate and self-limiting GI symptoms, including bloating, abdominal discomfort, flatulence, and transient diarrhea.<span class="xref"><span id="XREF_B108" class="ref-destination-back"></span><a href="#B108" data-id="XREF_B108" data-toggle="ref-popover" data-trigger="manual" data-placement="right">108</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B109" class="ref-destination-back"></span><a href="#B109" data-id="XREF_B109" data-toggle="ref-popover" data-trigger="manual" data-placement="right">109</a></span> Registry data suggest that short-term procedure-related complications are uncommon, occurring in fewer than 1% of cases in large cohorts.<span class="xref"><span id="XREF_B13" class="ref-destination-back"></span><a href="#B13" data-id="XREF_B13" data-toggle="ref-popover" data-trigger="manual" data-placement="right">13</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B110" class="ref-destination-back"></span><a href="#B110" data-id="XREF_B110" data-toggle="ref-popover" data-trigger="manual" data-placement="right">110</a></span> However, rare but serious adverse events can occur, underscoring the importance of stringent donor screening and quality control measures. A major safety concern in 2019 involved extended spectrum β-lactamase (ESBL)-producing <i>Escherichia coli</i>
697 bacteremia in two immunocompromised recipients after FMT from the same donor, including one death.<span class="xref"><span id="XREF_B111" class="ref-destination-back"></span><a href="#B111" data-id="XREF_B111" data-toggle="ref-popover" data-trigger="manual" data-placement="right">111</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B112" class="ref-destination-back"></span><a href="#B112" data-id="XREF_B112" data-toggle="ref-popover" data-trigger="manual" data-placement="right">112</a></span> Subsequent reports on enteropathogenic <i>E. coli</i> and Shiga toxin-producing <i>E. coli</i> (STEC) transmission raised concerns and prompted regulatory safety communications and enhanced screening requirements.<span class="xref"><span id="XREF_B113" class="ref-destination-back"></span><a href="#B113" data-id="XREF_B113" data-toggle="ref-popover" data-trigger="manual" data-placement="right">113</a></span> The most alarming finding was that the donor associated with STEC infections had previously tested negative for STEC by an immunoassay during fecal donation. However, when the recipient was found to be infected with STEC, the retained FMT sample tested positive for STEC by nucleic acid testing. These events highlight that periodic screening of donor feces, combined with a quarantine period and additional screening after international travel or temporary exclusion based on other indications, constitutes a reasonable strategy to prevent the release of fecal preparations that test positive for multidrug-resistant organisms (MDROs).<span class="xref"><span id="XREF_B14" class="ref-destination-back"></span><a href="#B14" data-id="XREF_B14" data-toggle="ref-popover" data-trigger="manual" data-placement="right">14</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B112" class="ref-destination-back"></span><a href="#B112" data-id="XREF_B112" data-toggle="ref-popover" data-trigger="manual" data-placement="right">112</a></span></p>
698<p>The long-term consequences of FMT remain unclear. The gut microbiome influences host metabolism, immunity, and potentially oncogenesis through complex mechanisms, raising theoretical concerns about the transmission of donor-associated phenotypes and the long-term effects of introducing exogenous microbial communities.<span class="xref"><span id="XREF_B13" class="ref-destination-back"></span><a href="#B13" data-id="XREF_B13" data-toggle="ref-popover" data-trigger="manual" data-placement="right">13</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B14" class="ref-destination-back"></span><a href="#B14" data-id="XREF_B14" data-toggle="ref-popover" data-trigger="manual" data-placement="right">14</a></span> Although registry-based follow-up studies have not identified major safety signals to date, continued surveillance is warranted as FMT applications expand.</p>
699</div>
700<div>
701<p class="article-section-sub-title article-section-sub-title-level-2"><h3>Donor screening and quality assurance</h3></p>
702<p>The preparation and screening of FMT products should be standardized. Current guidelines recommend comprehensive screening including detailed donor history and risk assessment, blood testing for transmissible infections (human immunodeficiency virus, hepatitis A, B, C, and syphilis), stool testing for bacterial pathogens, parasites, and viruses, and MDRO screening for ESBL-producing Enterobacteriaceae, vancomycin-resistant enterococci, carbapenem-resistant Enterobacteriaceae, and methicillin-resistant <i>Staphylococcus aureus</i> (<span class="fig-table-link"><a href="#T5">Table 5</a></span>).<span class="xref"><span id="XREF_B14" class="ref-destination-back"></span><a href="#B14" data-id="XREF_B14" data-toggle="ref-popover" data-trigger="manual" data-placement="right">14</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B114" class="ref-destination-back"></span><a href="#B114" data-id="XREF_B114" data-toggle="ref-popover" data-trigger="manual" data-placement="right">114</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B115" class="ref-destination-back"></span><a href="#B115" data-id="XREF_B115" data-toggle="ref-popover" data-trigger="manual" data-placement="right">115</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B116" class="ref-destination-back"></span><a href="#B116" data-id="XREF_B116" data-toggle="ref-popover" data-trigger="manual" data-placement="right">116</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B117" class="ref-destination-back"></span><a href="#B117" data-id="XREF_B117" data-toggle="ref-popover" data-trigger="manual" data-placement="right">117</a></span> Importantly, studies have shown that approximately 9% of healthy donor candidates test positive for MDROs, highlighting the need for systematic screening.<span class="xref"><span id="XREF_B118" class="ref-destination-back"></span><a href="#B118" data-id="XREF_B118" data-toggle="ref-popover" data-trigger="manual" data-placement="right">118</a></span> The results of this study indicate that MDRO colonization may remain in healthy donor feces, which are then quarantined or even preserved in the fecal bank. This has led to recommendations for quarantine peri
702ods during which donor samples are stored pending repeat testing, periodic rescreening of active donors, and nucleic acid-based testing methods that may be more sensitive than immunoassays for certain pathogens.<span class="xref"><span id="XREF_B119" class="ref-destination-back"></span><a href="#B119" data-id="XREF_B119" data-toggle="ref-popover" data-trigger="manual" data-placement="right">119</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B120" class="ref-destination-back"></span><a href="#B120" data-id="XREF_B120" data-toggle="ref-popover" data-trigger="manual" data-placement="right">120</a></span><div class="image-at-section"></div></p>
703<p><div class="article-table image-at-section"><div class="article-figure-table" id="T5"><div class="article-figure-table-card" id="TABLE-T5" data-type="T" data-afn="63_JKMS_41_38_e335" data-fn="jkms-41-e335-i005_0063JKMS"><div class="card border-0 my-3"><div class="row no-gutters">
704<div class="col-md-4 mx-auto d-flex justify-content-center flex-wrap align-middle"><div class="card-body">
705<a href="#" class="article-figure-table-btn" data-type="TH"><img class="align-top" src="/ArticleImage/0063JKMS/jkms-41-e335-i005-m.jpg"></a>
706</div></div>
707<div class="col-md-8"><div class="card-body">
708<p class="card-text"><span class="label"><a href="#" class="article-figure-table-btn" data-type="T">Table 5</a>
709</span><span class="capture-id"><br><span class="capture-id">Conditions and questionnaire to meet the screening criteria of donors for fecal microbiota transplantation</span></span></p>
710<ul class="list-inline">
711<li class="list-inline-item"><a role="button" class="btn btn-outline-article btn-sm article-figure-table-btn" data-type="T">Click for larger image</a></li>
712<li class="list-inline-item"><a role="button" class="btn btn-outline-article btn-sm article-figure-table-btn" data-type="TH">Click for full table</a></li>
713<li class="list-inline-item"><a role="button" class="btn btn-outline-article btn-sm" href="ViewImagePopup.php?Type=TX&amp;id=T5&amp;afn=63_JKMS_41_38_e335&amp;fn=jkms-41-e335-i005_0063JKMS" target="_blank">Download as Excel file</a></li>
714</ul>
715</div></div>
716</div></div></div></div></div></p>
717<p>During the coronavirus disease 2019 (COVID-19) pandemic, the U.S. Food and Drug Administration (FDA) issued additional safety communications recommending enhanced donor screening for SARS-CoV-2 infection together with molecular testing of stool or donor specimens where appropriate.<span class="xref"><span id="XREF_B121" class="ref-destination-back"></span><a href="#B121" data-id="XREF_B121" data-toggle="ref-popover" data-trigger="manual" data-placement="right">121</a></span> These recommendations highlighted that emerging infectious diseases may introduce previously unrecognized risks for FMT and emphasized the need for dynamic donor-screening protocols capable of adapting rapidly to newly identified pathogens. The COVID-19 experience further reinforced the importance of stool quarantine, traceability, and comprehensive quality assurance within stool-bank programs.</p>
718</div>
719</div>
720
721<div>
722<div><div class="article-section-header">
723<div class="__SECTION__" id="__ID_SECTION_7" data-section-name="REGULATORY FRAMEWORKS AND STANDARDIZATION"><div class="dropdown">
724<a href="#" class="dropdown-goto dropdown-toggle d-none" id="dropdownGoto_7" title="Go to other sections in this page" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">Go to:</a><div class="dropdown-menu dropdown-menu-right d-none" aria-labelledby="dropdownGoto_7"></div>
725</div></div>
726<h2>REGULATORY FRAMEWORKS AND STANDARDIZATION</h2>
727</div></div>
728<div>
729<p class="article-section-sub-title article-section-sub-title-level-2"><h3>Regulating the use of FMT</h3></p>
730<p>The regulatory oversight of stool used for FMT is clearly indicated. Although FMT has demonstrated an overall favorable safety profile to date, there is a risk of transfer of both known and unknown infectious pathogens from the donor to the recipient. Nevertheless, the regulatory classification of FMT varies widely across countries, reflecting different approaches to this novel therapeutic modality.<span class="xref"><span id="XREF_B122" class="ref-destination-back"></span><a href="#B122" data-id="XREF_B122" data-toggle="ref-popover" data-trigger="manual" data-placement="right">122</a></span>
730 FMT can be classified into four categories: an investigational drug (requiring clinical trial protocols), a tissue or transplant product, a medicinal product, and the practice of medicine with less stringent regulations.<span class="xref"><span id="XREF_B123" class="ref-destination-back"></span><a href="#B123" data-id="XREF_B123" data-toggle="ref-popover" data-trigger="manual" data-placement="right">123</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B124" class="ref-destination-back"></span><a href="#B124" data-id="XREF_B124" data-toggle="ref-popover" data-trigger="manual" data-placement="right">124</a></span> These classifications have important implications for access, safety, and commercialization.</p>
731<p>
732<span class="fig-table-link"><a href="#T6">Table 6</a></span> summarizes current classifications. FMT has been considered a medicine in the UK since 2015 and is now under the jurisdiction of the Medicines and Healthcare Products Regulatory Agency.<span class="xref"><span id="XREF_B125" class="ref-destination-back"></span><a href="#B125" data-id="XREF_B125" data-toggle="ref-popover" data-trigger="manual" data-placement="right">125</a></span> Beyond this classification, a working group of United European Gastroenterology considers stool a transplant product and urges the appropriate authorities to establish a comprehensive legal framework to ensure the safety and broad application of FMT.<span class="xref"><span id="XREF_B124" class="ref-destination-back"></span><a href="#B124" data-id="XREF_B124" data-toggle="ref-popover" data-trigger="manual" data-placement="right">124</a></span> The Therapeutic Goods Administration of Australia classifies FMT as a class 1 biologic product when obtained under supervision, advice, or compliance with regulations of a licensed medical practitioner, and as a class 2 biological product when it is made in a hospital and used in multiple hospitals or clinics, or when it is produced in a non-hospital facility with minimal alteration.<span class="xref"><span id="XREF_B126" class="ref-destination-back"></span><a href="#B126" data-id="XREF_B126" data-toggle="ref-popover" data-trigger="manual" data-placement="right">126</a></span> However, in low- and middle-income countries, the regulatory framework for microbiome-based therapies is underdeveloped, and there is a lack of specific guidelines or policies addressing the development, practice, and approval of FMT.<span class="xref"><span id="XREF_B127" class="ref-destination-back"></span><a href="#B127" data-id="XREF_B127" data-toggle="ref-popover" data-trigger="manual" data-placement="right">127</a></span><div class="image-at-section"></div></p>
733<p><div class="article-table image-at-section"><div class="article-figure-table" id="T6"><div class="article-figure-table-card" id="TABLE-T6" data-type="T" data-afn="63_JKMS_41_38_e335" data-fn="jkms-41-e335-i006_0063JKMS"><div class="card border-0 my-3"><div class="row no-gutters">
734<div class="col-md-4 mx-auto d-flex justify-content-center flex-wrap align-middle"><div class="card-body">
735<a href="#" class="article-figure-table-btn" data-type="TH"><img class="align-top" src="/ArticleImage/0063JKMS/jkms-41-e335-i006-m.jpg"></a>
736</div></div>
737<div class="col-md-8"><div class="card-body">
738<p class="card-text"><span class="label"><a href="#" class="article-figure-table-btn" data-type="T">Table 6</a>
739</span><span class="capture-id"><br><span class="capture-id">Regulatory classification of fecal microbiota transplantation</span></span></p>
740<ul class="list-inline">
741<li class="list-inline-item"><a role="button" class="btn btn-outline-article btn-sm article-figure-table-btn" data-type="T">Click for larger image</a></li>
742<li class="list-inline-item"><a role="button" class="btn btn-outline-article btn-sm article-figure-table-btn" data-type="TH">Click for full table</a></li>
743<li class="list-inline-item"><a role="button" class="btn btn-outline-article btn-sm" href="ViewImagePopup.php?Type=TX&amp;id=T6&amp;afn=63_JKMS_41_38_e335&amp;fn=jkms-41-e335-i006_0063JKMS" target="_blank">Download as Excel file</a></li>
744</ul>
745</div></div>
746</div></div></div></div></div></p>
747<p>The current FDA regulatory approach is based on enforcement discretion, permitting conventional donor-derived FMT for rC
747DI not responding to standard therapy provided that informed consent is obtained and appropriate donor screening is performed. This policy does not constitute formal approval of conventional FMT and has been in place since 2013 and remains limited to carefully defined clinical circumstances; it does not broadly extend to non-CDI indications or to unrestricted stool-bank distribution.</p>
748</div>
749<div>
750<p class="article-section-sub-title article-section-sub-title-level-2"><h3>Stool banks and standardization</h3></p>
751<p>Over the last decade, the safety and availability of FMT products have been modernized through a framework that improves access to donor fecal suspensions in several ways, including frozen feces, oral capsules, and stool banks.<span class="xref"><span id="XREF_B20" class="ref-destination-back"></span><a href="#B20" data-id="XREF_B20" data-toggle="ref-popover" data-trigger="manual" data-placement="right">20</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B128" class="ref-destination-back"></span><a href="#B128" data-id="XREF_B128" data-toggle="ref-popover" data-trigger="manual" data-placement="right">128</a></span> Frozen feces can replace fresh FMT products in large-volume FMT centers and provide an opportunity to develop stool biobanks.<span class="xref"><span id="XREF_B129" class="ref-destination-back"></span><a href="#B129" data-id="XREF_B129" data-toggle="ref-popover" data-trigger="manual" data-placement="right">129</a></span> Stool biobanks can reduce logistical burdens and improve traceability and quality control through standard operating procedures, quarantine-release procedures, and adverse event surveillance.<span class="xref"><span id="XREF_B130" class="ref-destination-back"></span><a href="#B130" data-id="XREF_B130" data-toggle="ref-popover" data-trigger="manual" data-placement="right">130</a></span> However, acceptance of stool bank models varies across different regulatory environments. Therefore, the establishment of regional stool bank networks will likely improve accessibility while maintaining consistent quality standards across institutions.</p>
752<p>A key transition in FMT regulation came with the U.S. FDA approval of standardized microbiota-based therapeutics.<span class="xref"><span id="XREF_B6" class="ref-destination-back"></span><a href="#B6" data-id="XREF_B6" data-toggle="ref-popover" data-trigger="manual" data-placement="right">6</a></span> REBYOTA (fecal microbiota live-jslm) is a live biotherapeutic product (LBP) composed of a broad consortium of microorganisms derived from human stools and delivered via enema. VOWST (fecal microbiota spores live-brpk) is a live microbiome therapeutic composed of live purified <i>Firmicutes</i> spores administered via the oral capsule. To avoid conceptual confusion, it is important to distinguish conventional donor-derived FMT from FDA-approved microbiota-based LBPs. Conventional FMT involves transplantation of minimally manipulated donor stools, whereas REBYOTA and VOWST are standardized microbiota-based therapeutics manufactured under Good Manufacturing Practice standards and approved specifically for the prevention of rCDI after completion of antibiotic therapy.<span class="xref"><span id="XREF_B6" class="ref-destination-back"></span><a href="#B6" data-id="XREF_B6" data-toggle="ref-popover" data-trigger="manual" data-placement="right">6</a></span> These developments have shifted the regulatory policy from experimental procedures to regulated biologics and may shape future pathways for microbiome therapeutics beyond CDI.</p>
753</div>
754<div>
755<p class="article-section-sub-title article-section-sub-title-level-2"><h3>Regional perspective</h3></p>
756<p>Korea has emerged as one of the leading countries in Asia for the clinical implementation of FMT through publication of national clinical practice guidelines and the gradual establishment of standardized donor screening protocols and stool bank infrastructure. The national multidisciplinary clinical practice guidelines for FMT were first published in 2022, which prioritized rCDI as the principal indication.<span class="xref"><span id="XREF_B14" class="ref-destination-back"></span><a href="#B14" data-id="XREF_B14" data-toggle="ref-popover" data-trigger="manual" data-placement="right">14</a></span> These guidelines defined donor screening and procedural standards adapted to the Korean healthcare setting. FMT was designated as New Medical Technologies in Korea 
756in June 2016, for recurrent or antibiotic-refractory CDI, under the national technology assessment pathway (including the innovative-technology/temporary-listing route) that evaluates safety, efficacy, and reimbursement eligibility.<span class="xref"><span id="XREF_B131" class="ref-destination-back"></span><a href="#B131" data-id="XREF_B131" data-toggle="ref-popover" data-trigger="manual" data-placement="right">131</a></span> Nevertheless, widespread implementation remains limited compared with that in several Western countries because of regulatory requirements, donor availability, and institutional resources.</p>
757<p>Operationally, non-profit fecal microbiota (stool) banks have been established in Korea, including a university-hospital-affiliated bank (MicrobiotiX Inc. and BioBankHealing Corp.) that provides pre-screened, frozen donor material.<span class="xref"><span id="XREF_B132" class="ref-destination-back"></span><a href="#B132" data-id="XREF_B132" data-toggle="ref-popover" data-trigger="manual" data-placement="right">132</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B133" class="ref-destination-back"></span><a href="#B133" data-id="XREF_B133" data-toggle="ref-popover" data-trigger="manual" data-placement="right">133</a></span> Donor screening by MicrobiotiX Inc. between 2017 and 2023 showed that only 5% of potential donors ultimately qualified for repeat donation, underscoring the stringency required for safe, standardized banking.<span class="xref"><span id="XREF_B134" class="ref-destination-back"></span><a href="#B134" data-id="XREF_B134" data-toggle="ref-popover" data-trigger="manual" data-placement="right">134</a></span></p>
758<p>Regional differences in efficacy signals for FMT have also been reported between Eastern and Western studies. Several Asian cohorts have shown favorable responses after single FMT administration for rCDI, whereas Western studies more frequently employed repeated or multidonor FMT protocols. Differences in circulating <i>C. difficile</i> strains, baseline gut microbiome composition, dietary patterns, and donor selection strategies could influence baseline severity, recurrence risk, and consequently the number of FMT sessions required to achieve durable resolution.<span class="xref"><span id="XREF_B52" class="ref-destination-back"></span><a href="#B52" data-id="XREF_B52" data-toggle="ref-popover" data-trigger="manual" data-placement="right">52</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B135" class="ref-destination-back"></span><a href="#B135" data-id="XREF_B135" data-toggle="ref-popover" data-trigger="manual" data-placement="right">135</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B136" class="ref-destination-back"></span><a href="#B136" data-id="XREF_B136" data-toggle="ref-popover" data-trigger="manual" data-placement="right">136</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B137" class="ref-destination-back"></span><a href="#B137" data-id="XREF_B137" data-toggle="ref-popover" data-trigger="manual" data-placement="right">137</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B138" class="ref-destination-back"></span><a href="#B138" data-id="XREF_B138" data-toggle="ref-popover" data-trigger="manual" data-placement="right">138</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B139" class="ref-destination-back"></span><a href="#B139" data-id="XREF_B139" data-toggle="ref-popover" data-trigger="manual" data-placement="right">139</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B140" class="ref-destination-back"></span><a href="#B140" data-id="XREF_B140" data-toggle="ref-popover" data-trigger="manual" data-placement="right">140</a></span> However, direct East–West comparisons of single- versus multiple-session efficacy remain limited by heterogeneous protocols and patient populations, and current data do n
758ot support a firm regional rule. These factors should therefore be regarded as hypothesis-generating, motivating region-stratified prospective studies rather than established determinants of efficacy.</p>
759</div>
760</div>
761
762<div>
763<div><div class="article-section-header">
764<div class="__SECTION__" id="__ID_SECTION_8" data-section-name="FUTURE DIRECTIONS"><div class="dropdown">
765<a href="#" class="dropdown-goto dropdown-toggle d-none" id="dropdownGoto_8" title="Go to other sections in this page" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">Go to:</a><div class="dropdown-menu dropdown-menu-right d-none" aria-labelledby="dropdownGoto_8"></div>
766</div></div>
767<h2>FUTURE DIRECTIONS</h2>
768</div></div>
769<p>Multiple clinical trials have evaluated FMT across diverse indications beyond CDI. Supplementary Table 3 summarizes the selected trials registered at ClinicalTrials.gov (accessed on January 12, 2026), highlighting the breadth of emerging applications, including IBD, metabolic disorders, and neurological conditions. Beyond the ongoing trials, several strategic priorities will shape the next phase of FMT research.</p>
770<p>First, the development of next-generation microbiome therapeutics, including defined bacterial consortia and microbiome-derived postbiotics, offers greater reproducibility and safety than whole-stool FMT. Products such as VE303, a rationally designed consortium of clonal bacterial strains, have demonstrated successful colonization and metabolome modulation in healthy volunteers, providing a template for indication-specific therapeutic development.<span class="xref"><span id="XREF_B141" class="ref-destination-back"></span><a href="#B141" data-id="XREF_B141" data-toggle="ref-popover" data-trigger="manual" data-placement="right">141</a></span></p>
771<p>Second, precision approaches to FMT have gained momentum. Biomarker-guided patient stratification, including baseline microbiome signatures that predict engraftment success and clinical response, may enable personalized donor-recipient matching and optimize therapeutic outcomes. Early evidence suggests that recipient microbiome composition at baseline influences the metabolic response to FMT, supporting the feasibility of predictive stratification.<span class="xref"><span id="XREF_B78" class="ref-destination-back"></span><a href="#B78" data-id="XREF_B78" data-toggle="ref-popover" data-trigger="manual" data-placement="right">78</a></span><span class="xref"><span class="gen">, </span><span id="XREF_B142" class="ref-destination-back"></span><a href="#B142" data-id="XREF_B142" data-toggle="ref-popover" data-trigger="manual" data-placement="right">142</a></span> Third, the optimal dose, frequency, route of administration, and maintenance strategy are likely to differ by indication. For chronic metabolic and neurological disorders, where treatment effects may be transient, repeated FMT and combination strategies with structured pharmacotherapy, dietary intervention, or behavioral modifications warrant systematic evaluation to improve therapeutic effects. This approach would be particularly beneficial in chronic metabolic and neurological conditions where single-intervention approaches have shown limited durability.</p>
772<p>Finally, the expansion of national and international registries will enable a robust real-world assessment of long-term efficacy and safety. As advances in the field take place, international collaboration through expanded registries will become essential for capturing real-world safety signals and long-term outcomes across diverse populations and indications. Harmonizing regulatory frameworks and enabling collaborative data sharing will accelerate progress in this field.</p>
773</div>
774
775<div>
776<div><div class="article-section-header">
777<div class="__SECTION__" id="__ID_SECTION_9" data-section-name="CONCLUSIONS"><div class="dropdown">
778<a href="#" class="dropdown-goto dropdown-toggle d-none" id="dropdownGoto_9" title="Go to other sections in this page" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">Go to:</a><div class="dropdown-menu dropdown-menu-right d-none" aria-labelledby="dropdownGoto_9"></div>
779</div></div>
780<h2>CONCLUSIONS</h2>
781</div></div>
782<p>FMT has evolved from an experimental approach to an evidence-based therapy for rCDI, validating microbiome restoration as a meaningful clinical strategy. Building on this foundation, FMT is increasingly being investigated beyond CDI, particularly in metabolic and neurological disorders, where dysbiosis and microbiome-driven immune and metabolite signaling contribute to disease biology. Current evidence in these emerging indications is promising, yet preliminary: metabolic 
782studies show improvements in insulin sensitivity but inconsistent durability that may depend on engraftment and dietary context, and neurological studies suggest modest benefits in selected outcomes with heterogeneous responses. Overall, the evidence base is heterogeneous and generally of lower certainty than that for rCDI. Trials differ substantially in patient populations and disease activity, donor selection (single vs. multidonor, universal vs. patient-directed), FMT preparation and dosing, routes of administration, maintenance strategies, outcome measures, and follow-up duration. These differences limit cross-study comparability and pooled interpretation. The application of FMT for conditions other than CDI requires the concurrent consideration of high-quality evidence, biological plausibility, safety, and standardization of the procedure.</p>
783<p>As the indications expand, safety and standardization become paramount. Rare but serious transmission of infectious pathogens has driven stringent donor screening and quality assurance, including MDRO testing and quarantine protocols. The regulatory landscape is also evolving, with a trend toward regulated biologics supported by the approval of standardized products for rCDI. Future progress will depend on mechanistically enriched trials, durable protocol strategies, biomarker-guided patient selection, and ultimately, a shift toward standardized, defined microbial therapeutics. With thoughtful regulations and sustained international collaboration, FMT and microbiome-based interventions may become important tools for realizing their therapeutic potential while ensuring patient safety.</p>
784</div>
785
786<div id="supplementary-material"><p><a id="#supplementary-material-sec" name="#supplementary-material-sec"></a>
787<div><div class="article-section-header">
788<div class="__SECTION__" id="__ID_SECTION_10" data-section-name="SUPPLEMENTARY MATERIALS"><div class="dropdown">
789<a href="#" class="dropdown-goto dropdown-toggle d-none" id="dropdownGoto_10" title="Go to other sections in this page" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">Go to:</a><div class="dropdown-menu dropdown-menu-right d-none" aria-labelledby="dropdownGoto_10"></div>
790</div></div>
791<h2>SUPPLEMENTARY MATERIALS</h2>
792</div></div>
793<p class="supplementary-material-item"><span class="capture-id">
794<h3>Supplementary Table 1</h3>
795<p>Correspondence of GRADE certainty of evidence with plain-language tier labels and their interpretations</p>
796</span><a href="DownloadSupplMaterial.php?id=10.3346/jkms.2026.41.e335&amp;fn=jkms-41-e335-s001.doc" id="S1">Click here to view.</a><sup class="supplementary-material-media-attribute">(31K, doc)</sup>
797</p><p class="supplementary-material-item"><span class="capture-id">
798<h3>Supplementary Table 2</h3>
799<p>Certainty of evidence for fecal microbiota transplantation across indications</p>
800</span><a href="DownloadSupplMaterial.php?id=10.3346/jkms.2026.41.e335&amp;fn=jkms-41-e335-s002.doc" id="S2">Click here to view.</a><sup class="supplementary-material-media-attribute">(38K, doc)</sup>
801</p><p class="supplementary-material-item"><span class="capture-id">
802<h3>Supplementary Table 3</h3>
803<p>Selected registered clinical trials (completed or active, not recruiting) of fecal microbiota transplantation beyond <i>C. difficile</i> infection (ClinicalTrials.gov)</p>
804</span><a href="DownloadSupplMaterial.php?id=10.3346/jkms.2026.41.e335&amp;fn=jkms-41-e335-s003.doc" id="S3">Click here to view.</a><sup class="supplementary-material-media-attribute">(44K, doc)</sup>
805</p></p></div>
806</div>
807
808<div id="article-level-0-figs-and-tables" class="bm bm-figure-tables">
809
810</div>
811
812<div id="article-level-0-back" class="bm">
813<div class="article-section-header">
814<div class="__SECTION__" id="__ID_SECTION_11" data-section-name="Notes"><div class="dropdown">
815<a href="#" class="dropdown-goto dropdown-toggle d-none" id="dropdownGoto_11" title="Go to other sections in this page" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">Go to:</a><div class="dropdown-menu dropdown-menu-right d-none" aria-labelledby="dropdownGoto_11"></div>
816</div></div>
817<div class="article-section-title">Notes</div>
818</div>
819<div id=""><p><span class="fn-label">Funding:</span>This research was supported by the Bio &amp; Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (No. RS-2023-00223501) and Hallym University Research Fund.</p></div>
820<div id=""><p><span class="fn-label">Disclosure:</span>The authors have no potential conflicts of interest to disclose.</p></div>
821<div id=""><p><span class="fn-label">Data Availability Statement:</span>Data sharing is not applicable as no new data were created or analyzed in this study.</p></div>
822<div id=""><p><span class="fn-label">Author Contributions:</span>
823<div>
824<ul class="listitem" style="list-style-type: none;">
825
826<li class="listitem"><p><b>Conceptualization:</b> Bang CS, Gong EJ, Lee JJ.</p></li>
827
828<li class="listitem"><p><b>Data curation:</b> Hasanuzzaman M, Gong EJ, Bang CS.</p></li>
829
830<li class="listitem"><p><b>Formal analysis:</b> Bang CS, Gong EJ.</p></li>
831
832<li class="listitem"><p><b>Funding acquisition:</b> Lee JJ.</p></li>
833
834<li class="listitem"><p><b>Investigation:</b> Hasanuzzaman M, Gong EJ.</p></li>
835
836<li class="listitem"><p><b>Methodology:</b> Bang CS, Gong EJ.</p></li>
837
838<li class="listitem"><p><b>Project administration:</b> Gong EJ, Lee JJ.</p></li>
839
840<li class="listitem"><p><b>Resources:</b> Lee JJ.</p></li>
841
842<li class="listitem"><p><b>Supervision:</b> Lee JJ.</p></li>
843
844<li class="listitem"><p><b>Visualization:</b> Hasanuzzaman M, Gong EJ.</p></li>
845
846<li class="listitem"><p><b>Writing - original draft:</b> Hasanuzzaman M, Bang CS.</p></li>
847
848<li class="listitem"><p><b>Writing - review &amp; editing:</b> Gong EJ, Lee JJ.</p></li>
849
850</ul>
851</div>
852</p></div>
853
854<div class="references">
855<div class="__SECTION__" id="__ID_SECTION_12" data-section-name="References"><div class="dropdown">
856<a href="#" class="dropdown-goto dropdown-toggle d-none" id="dropdownGoto_12" title="Go to other sections in this page" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">Go to:</a><div class="dropdown-menu dropdown-menu-right d-none" aria-labelledby="dropdownGoto_12"></div>
857</div></div>
858<h3 class="title">References</h3>
859</div>
860<div class="bm">
861<tr>
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863<td></td>
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2185<!--[KOREAMED SYNAPSE REFID:B134] *** BEGIN ***--><li class="list-group-item-ref"><a href="https://doi.org/10.5145%2FACM.2024.27.1.3" target="_new"><span>CrossRef</span></a></li>
2186<!--[KOREAMED SYNAPSE REFID:B134] *** END ***-->
2187</ul></div></span>
2188</div>
2189</li></ol></li>
2190<li><ol class="references-and-notes-list"><li class="skip-numbering" value="1">
2191<div id="B135" class="ref-destination"></div>
2192<div class="ref-item">
2193<span id="XREF_B135_DATA" class="ref-data" valign="top">Collins DA, Hawkey PM, Riley TV. Epidemiology of <i>Clostridium difficile</i> infection in Asia. Antimicrob Resist Infect Control 2013;2(1):21.<div><ul class="list-group list-group-horizontal">
2194<!--[KOREAMED SYNAPSE REFID:B135] *** BEGIN ***--><li class="list-group-item-ref"><a href="https://pubmed.ncbi.nlm.nih.gov/23816346" target="_new"><span>PubMed</span></a></li>
2195<li class="list-group-item-ref"><a href="https://doi.org/10.1186%2F2047-2994-2-21" target="_new"><span>CrossRef</span></a></li>
2196<!--[KOREAMED SYNAPSE REFID:B135] *** END ***-->
2197</ul></div></span>
2198</div>
2199</li></ol></li>
2200<li><ol class="references-and-notes-list"><li class="skip-numbering" value="1">
2201<div id="B136" class="ref-destination"></div>
2202<div class="ref-item">
2203<span id="XREF_B136_DATA" class="ref-data" valign="top">Bauer MP, Notermans DW, van Benthem BH, Brazier JS, Wilcox MH, Rupnik M, et al. 
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2205<!--[KOREAMED SYNAPSE REFID:B136] *** BEGIN ***--><li class="list-group-item-ref"><a href="https://pubmed.ncbi.nlm.nih.gov/21084111" target="_new"><span>PubMed</span></a></li>
2206<li class="list-group-item-ref"><a href="https://doi.org/10.1016%2FS0140-6736%2810%2961266-4" target="_new"><span>CrossRef</span></a></li>
2207<!--[KOREAMED SYNAPSE REFID:B136] *** END ***-->
2208</ul></div></span>
2209</div>
2210</li></ol></li>
2211<li><ol class="references-and-notes-list"><li class="skip-numbering" value="1">
2212<div id="B137" class="ref-destination"></div>
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2214<span id="XREF_B137_DATA" class="ref-data" valign="top">Kim J, Kang JO, Kim H, Seo MR, Choi TY, Pai H, et al. Epidemiology of <i>Clostridium difficile</i>
2214 infections in a tertiary-care hospital in Korea. Clin Microbiol Infect 2013;19(6):521–527.<div><ul class="list-group list-group-horizontal">
2215<!--[KOREAMED SYNAPSE REFID:B137] *** BEGIN ***--><li class="list-group-item-ref"><a href="https://pubmed.ncbi.nlm.nih.gov/22712697" target="_new"><span>PubMed</span></a></li>
2216<li class="list-group-item-ref"><a href="https://doi.org/10.1111%2Fj.1469-0691.2012.03910.x" target="_new"><span>CrossRef</span></a></li>
2217<!--[KOREAMED SYNAPSE REFID:B137] *** END ***-->
2218</ul></div></span>
2219</div>
2220</li></ol></li>
2221<li><ol class="references-and-notes-list"><li class="skip-numbering" value="1">
2222<div id="B138" class="ref-destination"></div>
2223<div class="ref-item">
2224<span id="XREF_B138_DATA" class="ref-data" valign="top">Wei S, Bahl MI, Baunwall SMD, Dahlerup JF, Hvas CL, Licht TR. Gut microbiota differs between treatment outcomes early after fecal microbiota transplantation against recurrent <i>Clostridioides difficile</i> infection. Gut Microbes 2022;14(1):2084306<div><ul class="list-group list-group-horizontal">
2225<!--[KOREAMED SYNAPSE REFID:B138] *** BEGIN ***--><li class="list-group-item-ref"><a href="https://pubmed.ncbi.nlm.nih.gov/36519447" target="_new"><span>PubMed</span></a></li>
2226<li class="list-group-item-ref"><a href="https://doi.org/10.1080%2F19490976.2022.2084306" target="_new"><span>CrossRef</span></a></li>
2227<!--[KOREAMED SYNAPSE REFID:B138] *** END ***-->
2228</ul></div></span>
2229</div>
2230</li></ol></li>
2231<li><ol class="references-and-notes-list"><li class="skip-numbering" value="1">
2232<div id="B139" class="ref-destination"></div>
2233<div class="ref-item">
2234<span id="XREF_B139_DATA" class="ref-data" valign="top">David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 2014;505(7484):559–563.<div><ul class="list-group list-group-horizontal">
2235<!--[KOREAMED SYNAPSE REFID:B139] *** BEGIN ***--><li class="list-group-item-ref"><a href="https://pubmed.ncbi.nlm.nih.gov/24336217" target="_new"><span>PubMed</span></a></li>
2236<li class="list-group-item-ref"><a href="https://doi.org/10.1038%2Fnature12820" target="_new"><span>CrossRef</span></a></li>
2237<!--[KOREAMED SYNAPSE REFID:B139] *** END ***-->
2238</ul></div></span>
2239</div>
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2241<li><ol class="references-and-notes-list"><li class="skip-numbering" value="1">
2242<div id="B140" class="ref-destination"></div>
2243<div class="ref-item">
2244<span id="XREF_B140_DATA" class="ref-data" valign="top">Baunwall SMD, Lee MM, Eriksen MK, Mullish BH, Marchesi JR, Dahlerup JF, et al. Faecal microbiota transplantation for recurrent <i>Clostridioides difficile</i> infection: An updated systematic review and meta-analysis. EClinicalMedicine 2020;29-30:100642<div><ul class="list-group list-group-horizontal">
2245<!--[KOREAMED SYNAPSE REFID:B140] *** BEGIN ***--><li class="list-group-item-ref"><a href="https://pubmed.ncbi.nlm.nih.gov/33437951" target="_new"><span>PubMed</span></a></li>
2246<li class="list-group-item-ref"><a href="https://doi.org/10.1016%2Fj.eclinm.2020.100642" target="_new"><span>CrossRef</span></a></li>
2247<!--[KOREAMED SYNAPSE REFID:B140] *** END ***-->
2248</ul></div></span>
2249</div>
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2251<li><ol class="references-and-notes-list"><li class="skip-numbering" value="1">
2252<div id="B141" class="ref-destination"></div>
2253<div class="ref-item">
2254<span id="XREF_B141_DATA" class="ref-data" valign="top">Dsouza M, Menon R, Crossette E, Bhattarai SK, Schneider J, Kim YG, et al. Colonization of the live biotherapeutic product VE303 and modulation of the microbiota and metabolites in healthy volunteers. Cell Host Microbe 2022;30(4):583–598.e8.<div><ul class="list-group list-group-horizontal">
2255<!--[KOREAMED SYNAPSE REFID:B141] *** BEGIN ***--><li class="list-group-item-ref"><a href="https://pubmed.ncbi.nlm.nih.gov/35421353" target="_new"><span>PubMed</span></a></li>
2256<li class="list-group-item-ref"><a href="https://doi.org/10.1016%2Fj.chom.2022.03.016" target="_new"><span>CrossRef</span></a></li>
2257<!--[KOREAMED SYNAPSE REFID:B141] *** END ***-->
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2259</div>
2260</li></ol></li>
2261<li><ol class="references-and-notes-list"><li class="skip-numbering" value="1">
2262<div id="B142" class="ref-destination"></div>
2263<div class="ref-item">
2264<span id="XREF_B142_DATA" class="ref-data" valign="top">Kang GU, Park S, Jung Y, Jee JJ, Kim MS, Lee S, et al. Exploration of potential gut microbiota-derived biomarkers to predict the success of fecal microbiota transplantation in ulcerative colitis: a prospective cohort in Korea. Gut Liver 2022;
226416(5):775–785.<div><ul class="list-group list-group-horizontal">
2265<!--[KOREAMED SYNAPSE REFID:B142] *** BEGIN ***--><li class="list-group-item-ref"><a href="https://pubmed.ncbi.nlm.nih.gov/35975640" target="_new"><span>PubMed</span></a></li>
2266<li class="list-group-item-ref"><a href="https://doi.org/10.5009%2Fgnl210369" target="_new"><span>CrossRef</span></a></li>
2267<!--[KOREAMED SYNAPSE REFID:B142] *** END ***-->
2268</ul></div></span>
2269</div>
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2327                    <span class="align-top">Supplementary Materials</span>
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2330                                        
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2354                <h5>Publication Types</h5>
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2356
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2358            <div class="chip text-truncate my-1 mr-1">Review</div>            
2359            </div>
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2361        
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2363            <div class="my-3">
2364                <h5>MeSH Terms</h5>
2365            </div>
2366
2367            <div class="d-inline-flex flex-wrap material-chips">
2368            <div class="chip text-truncate my-1 mr-1"><a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Biological+Products%22%5BMeSH+Terms%5D" target="_blank">Biological Products</a></div><div class="chip text-truncate my-1 mr-1"><a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Biomarkers%22%5BMeSH+Terms%5D" target="_blank">Biomarkers</a></div><div class="chip text-truncate my-1 mr-1"><a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Clostridium+Infections%2A%22%5BMeSH+Major+Topic%5D" target="_blank">Clostridium Infections*</a></div><div class="chip text-truncate my-1 mr-1"><a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Dysbiosis%22%5BMeSH+Terms%5D" target="_blank">Dysbiosis</a></div><div class="chip text-truncate my-1 mr-1"><a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Fecal+Microbiota+Transplantation%2A%22%5BMeSH+Major+Topic%5D" target="_blank">Fecal Microbiota Transplantation*</a></div><div class="chip text-truncate my-1 mr-1"><a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Homeostasis%22%5BMeSH+Terms%5D" target="_blank">Homeostasis</a></div><div class="chip text-truncate my-1 mr-1"><a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Humans%22%5BMeSH+Terms%5D" target="_blank">Humans</a></div><div class="chip text-truncate my-1 mr-1"><a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Inflammatory+Bowel+Diseases%22%5BMeSH+Terms%5D" target="_blank">Inflammatory Bowel Diseases</a></div><div class="chip text-truncate my-1 mr-1"><a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Irritable+Bowel+Syndrome%22%5BMeSH+Terms%5D" target="_blank">Irritable Bowel Syndrome</a></div><div class="chip text-truncate my-1 mr-1">
2368<a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Metabolic+Diseases%2A%22%5BMeSH+Major+Topic%5D" target="_blank">Metabolic Diseases*</a></div><div class="chip text-truncate my-1 mr-1"><a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Metabolism%22%5BMeSH+Terms%5D" target="_blank">Metabolism</a></div><div class="chip text-truncate my-1 mr-1"><a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Microbiota%22%5BMeSH+Terms%5D" target="_blank">Microbiota</a></div><div class="chip text-truncate my-1 mr-1"><a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Nervous+System+Diseases%22%5BMeSH+Terms%5D" target="_blank">Nervous System Diseases</a></div><div class="chip text-truncate my-1 mr-1"><a href="https://pubmed.ncbi.nlm.nih.gov/?term=%22Neuroinflammatory+Diseases%2A%22%5BMeSH+Major+Topic%5D" target="_blank">Neuroinflammatory Diseases*</a></div>            
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2588                        <a href="https://orcid.org/0000-0001-7132-3921" data-toggle="tooltip" data-placement="right" title="https://orcid.org/0000-0001-7132-3921"><span class="align-middle pr-1 text-primary">Md Hasanuzzaman</span>&nbsp;<img src="image/icon-orcid.jpg" border="0" align="absmiddle"></a>
2589                    </li>
2590                                                        <li>
2591                        <a href="https://orcid.org/0000-0003-4908-5431" data-toggle="tooltip" data-placement="right" title="https://orcid.org/0000-0003-4908-5431"><span class="align-middle pr-1 text-primary">Chang Seok Bang</span>&nbsp;<img src="image/icon-orcid.jpg" border="0" align="absmiddle"></a>
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2595                    </li>
2596                                                        <li>
2597                        <a href="https://orcid.org/0000-0003-3996-3472" data-toggle="tooltip" data-placement="right" title="https://orcid.org/0000-0003-3996-3472"><span class="align-middle pr-1 text-primary">Eun Jeong Gong</span>&nbsp;<img src="image/icon-orcid.jpg" border="0" align="absmiddle"></a>
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2619                            <span class="text-primary">National Research Foundation of Korea</span>
2620                        </a>
2621                        						<div>RS-2023-00223501</div>
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2625                            <span class="text-primary">Hallym University</span>
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2942         </div>
2943         <div class="toast-footer text-end pe-2 py-2 border-0">
2944            <button type="botton" class="btn border closeBtn p-0" data-bs-dismiss="toast" OnClick="popup_closeWin2()"><span style="font-size: 0.7rem!important">Close</span><span class="d-block">for today</span></button>
2945         </div>
2946       </div>
2947     </div>
2948
2949</div> -->
2950
2951
2952
2953<script type="text/javascript">
2954// cookie에 Notice=done;을 추가
2955
2956function popup_closeWin()
2957{         
2958        console.log('add cookie Popup=done')
2959        popup_setcookie( "Popup", "done" , 1); // 하루동안 열지 않음.
2960        //self.close();
2961        //버튼 안보이게 숨기기
2962        //document.querySelector(".popupModalBtn").style.display = 'none';
2963        document.querySelector(".btnFixedTop").style.display = 'none';
2964}
2965
2966
2967function popup_closeWin2()
2968{         
2969        console.log('add cookie Popup2=done')
2970        popup_setcookie( "Popup2", "done" , 1); // 하루동안 열지 않음.
2971        //self.close();
2972        //버튼 안보이게 숨기기
2973        //document.querySelector(".popupModalBtn").style.display = 'none';
2974        document.querySelector(".btnFixedTop.notice2").style.display = 'none';
2975}
2976
2977function popup_setcookie( name, value, expiredays )
2978{   
2979    var todayDate = new Date();
2980    todayDate.setDate( todayDate.getDate() + expiredays );
2981    document.cookie = name + "=" + escape( value ) + "; path=/; expires=" + todayDate.toGMTString() + ";"
2982}
2983
2984function closeWin()
2985{         
2986        document.querySelector(".btnFixedTop").style.display = 'none';
2987}
2988
2989function closeWin2()
2990{         
2991        document.querySelector(".btnFixedTop.notice2").style.display = 'none';
2992}
2993
2994function na_call(str){  eval(str);}
2995
2996
2997//pop up
2998// const day = new Date();
2999// let popTodayHours = day.getHours();
3000
3001function popup_getcookie( name ){
3002   var nameOfcookie = name + "=";
3003   var x = 0;
3004   while ( x <= document.cookie.length )
3005   {
3006           var y = (x+nameOfcookie.length);
3007           if ( document.cookie.substring( x, y ) == nameOfcookie ) {
3008                   if ( (endOfcookie=document.cookie.indexOf( ";", y )) == -1 )
3009                           endOfcookie = document.cookie.length;
3010                   return unescape( document.cookie.substring( y, endOfcookie ) );
3011           }
3012           x = document.cookie.indexOf( " ", x ) + 1;
3013           if ( x == 0 )
3014                   break;
3015   }
3016   return "";
3017   console
3018}
3019
3020// 팝업 노출 시간 지정
3021// 목표 날짜 및 시간을 설정합니다 (2025년 12월 1일 00:00:00)
3022// const targetDate = new Date("2025-12-01T00:00:00");
3023
3024// // 현재 시간을 가져옵니다
3025// const now = new Date();
3026
3027// // 타겟 요소 선택
3028// const fixedElement = document.querySelector(".btnFixedTop");
3029
3030// // fixedElement가 존재하고, 현재 시간이 목표 날짜 이전이라면 요소를 숨깁니다.
3031// if (fixedElement && now < targetDate) {
3032//     fixedElement.style.display = 'none';
3033    
3034//     // (선택 사항) 요소가 성공적으로 숨겨졌는지 콘솔에 기록합니다.
3035//     console.log("팝업 숨김: 2025년 12월 1일 00:00:00 이전입니다.");
3036// }
3037
3038
3039
3040// cookie에 Notice=done;이 있으면 안보이게
3041if ( popup_getcookie( "Popup" ) == "done" ){
3042
3043       //document.querySelector(".popupModalBtn").style.display = 'block';
3044       document.querySelector(".btnFixedTop").style.display = 'none';
3045
3046}
3047
3048if ( popup_getcookie( "Popup2" ) == "done" ){
3049
3050       //document.querySelector(".popupModalBtn").style.display = 'block';
3051       document.querySelector(".btnFixedTop.notice2").style.display = 'none';
3052
3053}
3054
3055
3056/*팝업 리사이즈*/
3057// let pageHeight = document.body.scrollHeight + 75
3058// window.resizeTo(420,pageHeight);
3059
3060</script>
3060
3061
3062
3063
3064        </footer>        
3065
3066        <!-- Scripts -->
3067        
3068        
3068<script src="https://ajax.googleapis.com/ajax/libs/jquery/3.6.4/jquery.min.js"></script>
3068        
3069        
3069<script src="https://cdn.jsdelivr.net/npm/[email protected]/dist/js/bootstrap.bundle.min.js" integrity="sha384-YvpcrYf0tY3lHB60NNkmXc5s9fDVZLESaAA55NDzOxhy9GkcIdslK1eN7N6jIeHz" crossorigin="anonymous"></script>
3069
3070        
3070<script src="https://cdn.jsdelivr.net/gh/kartik-v/[email protected]/js/bootstrap-popover-x.min.js" type="text/javascript"></script>
3070
3071        
3071<script src="js/jquery.twbsPagination.min.js" type="text/javascript"></script>
3071
3072        
3072<script src="js/nouislider.min.js" type="text/javascript"></script>
3072
3073        
3073<script src="js/wNumb.min.js" type="text/javascript"></script>
3073
3074
3075        
3076    
3076<script src="js/chartist.min.js" type="text/javascript"></script>
3076
3077    
3077<script src="js/chartist-plugin-tooltip.js" type="text/javascript"></script>
3077
3078
3079    
3079<script src="js/commonScript.js" type="text/javascript"></script>
3079
3080    
3080<script src="js/sharepopoverScript.js" type="text/javascript" defer></script>
3080
3081    
3081<script src="js/refpopoverScript.js" type="text/javascript" defer></script>
3081
3082    
3082<script>
3083
3084        jQuery(document).ready(function ($) {
3085
3086            // Tooltip
3087            const tooltipTriggerList = document.querySelectorAll('[data-bs-toggle="tooltip"]');
3088            const tooltipList = [...tooltipTriggerList].map(tooltipTriggerEl => new bootstrap.Tooltip(tooltipTriggerEl));            
3089
3090                        $("#SharePermalinkText").val("https://jkms.org/DOIx.php?id=10.3346/jkms.2026.41.e335");
3091            
3092            // Icons
3093            const articleIconCoressp = document.getElementsByClassName("article-icon-corresp");
3094            for (let i = 0; i < articleIconCoressp.length; i++) {
3095                 articleIconCoressp[i].classList.add('bi', 'bi-envelope' );
3096            }
3097
3098                            // Document Type
3099            document.getElementsByClassName("article-type")[0].innerHTML = "Review Article";
3100                        
3101            //
3102            // Relate Articles
3103            //
3104
3105            const aRelateArticleInfo = [];            
3106            const articleRelateNode = document.getElementById("article-relate-articles");
3107            if  ( articleRelateNode != null ) {
3108                articleRelateNode.classList.add('list-group', 'my-3');
3109                for (index in aRelateArticleInfo) {
3110                    let div = document.createElement('div');
3111                    div.setAttribute('class', 'list-group-item');                
3112                    div.innerHTML  = aRelateArticleInfo[ index ];
3113                    articleRelateNode.appendChild ( div );
3114                }
3115            }
3116
3117            //
3118            // SCRIPTS
3119            //
3120
3121            //
3122            // for Authors and Keywords
3123            //
3124
3125            // Function to transform keywords into links
3126            function transformKeywords() {
3127                var keywordTitles = document.querySelectorAll('.article-keyword-group-title');
3128                keywordTitles.forEach(function (keywordTitle) {
3129                    var keywordContainer = keywordTitle.nextElementSibling;
3130                    if (keywordContainer) {
3131                    var keywordElements = keywordContainer.querySelectorAll('.capture-id');
3132                    keywordElements.forEach(function (element) {
3133                        var keyword = element.textContent.trim();
3134                        var link = document.createElement('a');
3135                        link.href = '/search.php?where=asummary&queryfilter=keyword&query=' + encodeURIComponent(keyword);
3136                        link.textContent = keyword;
3137                        element.innerHTML = '';
3138                        element.appendChild(link);
3139                        element.classList.add('keyword-group-item');
3140                    });
3141                    }
3142                });
3143            }
3144
3145            // transformKeywords();
3146
3147            var articleContrib = document.querySelector('.article-contrib');
3148            var nodes = articleContrib.childNodes;
3149
3150            if ($(".article-contrib .capture-id").length > 6) 
3151            {
3152                for (var i = 0; i < nodes.length; i++) {
3153                    if (nodes[i].nodeType === Node.TEXT_NODE && nodes[i].nodeValue.trim() === 'and') {
3154                        var span = document.createElement('span');
3155                        span.style.display = 'none';
3156                        span.className = 'hidden-and-text';
3157                        span.textContent = ' and ';
3158                        articleContrib.replaceChild(span, nodes[i]);
3159                        break;
3160                    }
3161                }
3162            }
3163
3164            function applyShowMore(selector) {
3165                $(selector + " .capture-id").each(function (index) {
3166                    if (index > 5) {
3167                        $(this).hide();
3168                    }
3169                });
3170
3171                if ($(selector + " .capture-id").length > 6) {
3172                    $(selector).append('<a href="#" class="show-more show-toggle">view all</a>');
3173                }
3174
3175                $(selector).on("click", ".show-more", function (e) {
3176                    e.preventDefault();
3177                    $(selector + " .capture-id:hidden").show();
3178                    if (selector === ".article-contrib") {
3179                        $(".hidden-and-text").show();
3180                    }
3181                    $(this).text(" view less ").removeClass("show-more").addClass("show-less");
3182                });
3183
3184                $(selector).on("click", ".show-less", function (e) {
3185                    e.preventDefault();
3186                    $(selector + " .capture-id").slice(6).hide();
3187                    if (selector === ".article-contrib") {
3188                        $(".hidden-and-text").hide();
3189                    }
3190                    $(this).text("view all").removeClass("show-less").addClass("show-more");
3191                });
3192            }
3193
3194            applyShowMore(".article-contrib");
3195            applyShowMore(".article-contrib-ko");            
3196
3197
3198            //
3199            // for SECTIONS
3200            //
3201
3202            var	aArticleSection = new  Array();            
3203            
3204            $( ".__SECTION__" ).each(function( index, elem ){
3205                aArticleSection.push(  $(elem).attr('data-section-name') );
3206			});
3207
3208            $( ".__SECTION__" ).each(function( index, elem ){
3209                var $dropdownMenuNode = $(elem).children(".dropdown").find(".dropdown-menu");
3210                $( aArticleSection ).each(function( index, elem ){
3211                    $dropdownMenuNode.append('<a class="dropdown-item" href="#__ID_SECTION_'+index+'">'+ elem +'</a>');
3212                });
3213            });
3214            
3215            $( aArticleSection ).each(function( index, elem ){
3216                $( '#navbar-goto-item' ).append('<li class="nav-item"><a class="nav-link" href="#__ID_SECTION_'+index+'">'+ elem +'</a></li>');
3217                $( '#navbar-article-top-toolbar-goto' ).append('<li><a class="dropdown-item" href="#__ID_SECTION_'+index+'">'+ elem +'</a></li>');
3218            });
3219
3220            function    moveArticleToSection( targetElement ) {
3221                var headerHeight = parseInt(getComputedStyle(document.querySelector('header')).height);
3222                var navbarArticleTopToolbarHeight = parseInt(getComputedStyle(document.querySelector('#navbar-article-top-toolbar')).height);
3223
3224                                var scrollDirection = targetElement.offsetTop > window.pageYOffset ? navbarArticleTopToolbarHeight + 15 : headerHeight + 15;
3225                window.scrollTo({ 
3226                    top: targetElement.offsetTop - scrollDirection ,
3227                    behavior: 'auto' 
3228                });
3229                            }
3230
3231            document.querySelectorAll('#navbar-article-top-toolbar-goto a[href^="#__ID_SECTION_"]').forEach(anchor => { 
3232                anchor.addEventListener('click', function (e) { 
3233                    e.preventDefault(); 
3234                    const targetElement = document.querySelector(this.getAttribute('href')); 
3235                    moveArticleToSection ( targetElement );
3236                }); 
3237            });
3238
3239            const moveArticleToSectionNode = document.querySelector('#article-move-supplement-material');
3240            if  ( moveArticleToSectionNode != null ) {
3241                moveArticleToSectionNode.addEventListener('click', function (e) { 
3242                    e.preventDefault(); 
3243                    const targetElement = document.querySelector(moveArticleToSectionNode.getAttribute('href')); 
3244                    moveArticleToSection ( targetElement );
3245                });
3246            }
3247        
3248            const scrollSpyTop = new bootstrap.ScrollSpy(document.body, {
3249                target: '#navbar-article-top-toolbar',
3250                });
3251
3252            const scrollSpyPortlet = new bootstrap.ScrollSpy(document.body, {
3253                target: '#navbar-goto',
3254                });
3255
3256
3257            if  ( aArticleSection.length > 1 ) {
3258                $(".navbar-goto-display").removeClass("d-none");
3259            }           
3260
3261            //
3262            // for CROSSMARK
3263            //
3264
3265                            $( "#crossref-crossmark a" ).append('<img src="https://crossmark-cdn.crossref.org/widget/v2.0/logos/CROSSMARK_Color_square.svg" width="60" />');
3266                $( "#crossref-crossmark" ).show();
3267                        
3268
3269            //
3270            //
3271            //
3272            
3273                        
3274			var aPageViewCount = {
3275					labels: ['Oct/2026'],
3276					series: [
3277						[{meta:'Oct/2026', value: 79}],						
3278					]
3279				};
3280
3281            var aPDFDownloadCount = {
3282                labels: ['Oct/2026'],
3283                series: [
3284                    [{meta:'Oct/2026', value: 13}],						
3285                ]
3286            };
3287
3288            $(".PageViewLink").on("click", function(){
3289
3290                new Chartist.Line('#my-chart', aPageViewCount, {
3291                    plugins: [
3292                        Chartist.plugins.tooltip({
3293                            pointClass: 'ct-point',
3294                            tooltipOffset: {
3295                                x: 15,
3296                                y: 35
3297                            },
3298                            transformTooltipTextFnc: function(value){
3299                                return	'Counts: ' + value;
3300                            }
3301                        })
3302                    ],
3303                    fullWidth: false,
3304                    lineSmooth: Chartist.Interpolation.cardinal({
3305                        tension: 0
3306                    }),						
3307                    low: 0,
3308                    showArea: true,
3309                    axisY: {
3310                        onlyInteger: true,
3311                        }
3312                    });
3313
3314                $('#myModalLabel').html('Page Views');
3315                $('#myModalTotalLinkLabel').html('<div class="d-flex">\
3316                    <div class="flex-grow-1">Total Page Views: 79</div><div><a href="/export/count/view/article/10.3346/jkms.2026.41.e335"><img src="image/icon-excel.png"> Download as Excel file</a></div>\
3317                    </div>\
3318                ');
3319
3320                var myModal = new bootstrap.Modal(document.getElementById('myModal'));                
3321                myModal.show();
3322
3323                return	false;
3324            });
3325
3326            $(".PDFDownloadLink").on("click", function(){
3327                new Chartist.Line('#my-chart', aPDFDownloadCount, {
3328                    fullWidth: false,
3329                    low: 0,
3330                    lineSmooth: Chartist.Interpolation.cardinal({
3331                        tension: 0
3332                    }),
3333                    showArea: true,
3334                    axisY: {
3335                        onlyInteger: true,							
3336                    },
3337                    plugins: [
3338                        Chartist.plugins.tooltip({
3339                            pointClass: 'ct-point',
3340                            tooltipOffset: {
3341                                x: 15,
3342                                y: 35
3343                            },
3344                            transformTooltipTextFnc: function(value){
3345                                return	'Counts: ' + value;
3346                            }
3347                        })
3348                    ],
3349                    });
3350
3351                $('#myModalLabel').html('PDF Downloads');
3352                $('#myModalTotalLinkLabel').html('<div class="d-flex"><div class="flex-grow-1">Total PDF Downloads: 13</div><div><a href="/export/count/download/pdf/10.3346/jkms.2026.41.e335"><img src="image/icon-excel.png"> Download as Excel file</a></div></div>');
3353
3354                var myModal = new bootstrap.Modal(document.getElementById('myModal'));                
3355                myModal.show();
3356
3357                return	false;
3358            });
3359
3360
3361            $("#item-list li").click(function(e) {
3362	            e.preventDefault();
3363	            e.stopPropagation();
3364            });
3365
3366            $('.bm-ref-list-ol > li').css("cursor", "pointer"); //addClass('link');
3367
3368            $(".bm-ref-list-ol li").on( "click", function() {                
3369                return false;
3370            }).children().click(function(e) {
3371                return false;
3372            }); 
3373        });
3374
3375
3376        var trackDownloadLink = function(category, doi) {
3377            gtag('event', 'download', {
3378                    'event_category': category,
3379                    'event_label': doi
3380                    });
3381        }
3382
3383
3384    </script>
3384
3385
3386        
3386<script src="https://crossmark-cdn.crossref.org/widget/v2.0/widget.js" type="text/javascript"></script>
3386
3387       
3388    
3389    
3389<script id="MathJax-script" async src="https://cdn.jsdelivr.net/npm/mathjax@3/es5/tex-mml-chtml.js"></script>
3389
3390
3391
3392        
3392<script type="text/javascript">
3393
3394
3395    // pop up
3396    // const day = new Date();
3397    // let todayHours1 = day.getHours();
3398
3399
3400    // function notice_getcookie1( name ){
3401    //     var nameOfcookie = name + "=";
3402    //     var x = 0;
3403    //     while ( x <= document.cookie.length )
3404    //     {
3405    //             var y = (x+nameOfcookie.length);
3406    //             if ( document.cookie.substring( x, y ) == nameOfcookie ) {
3407    //                     if ( (endOfcookie=document.cookie.indexOf( ";", y )) == -1 )
3408    //                             endOfcookie = document.cookie.length;
3409    //                     return unescape( document.cookie.substring( y, endOfcookie ) );
3410    //             }
3411    //             x = document.cookie.indexOf( " ", x ) + 1;
3412    //             if ( x == 0 )
3413    //                     break;
3414    //     }
3415    //     return "";
3416    // }
3417
3418    // if ( notice_getcookie( "Notice1" ) != "done1" )
3419    //     {
3420    //         // 연휴 공지
3421    //         popup2=window.open("notice_20231228.html","popup2","scrollbars=no,toolbar=no,width=405,height=275,left=100,top=100")
3422
3423    //     }
3424
3425
3426</script>
vendor: 1 bytes, line 3426
3426
3427<script src="js/ga_modal.js"></script>
vendor: 1 bytes, line 3427
3427
3428<script src="js/article_modal.js"></script>
vendor: 1 bytes, line 3428
3428
3429<script src="js/forthcomingAdd.js?v=20260724"></script>
vendor: 1 bytes, line 3429
3429
3430<script src="js/add_poll.js?v=20261008"></script>
vendor: 1 bytes, line 3430
3430
3431<script src="js/add_summary.js"></script>
vendor: 1 bytes, line 3431
3431
3432<script src="js/add_summary-add.js"></script>
vendor: 1 bytes, line 3432
3432
3433<script src="js/sortArchive.js"></script>
vendor: 1 bytes, line 3433
3433
3434<script src="js/scroll_change_menu.js"></script>
vendor: 1 bytes, line 3434
3434
3435<script src="js/modifyArticle.js"></script>
vendor: 1 bytes, line 3435
3435
3436<script src="https://xmlink.kr/js/image_slider.js"></script>
vendor: 1 bytes, line 3436
3436
3437<script src="https://xmlink.kr/js/sliderControl.js"></script>
vendor: 1 bytes, line 3437
3437
3438<script src="https://xmlink.kr/js/metricsAdd.js"></script>
3438
3439
3440</script>
3440
3441<!-- 
3441<script src="js/covid_select.js"></script>
3441 -->
3442<!-- 
3442<script src="js/changeInfo.js"></script>
vendor: 1 bytes, line 3442
3442
3443<script src="js/modifyArticle.js"></script>
3443 -->
3444    
3444<script>document.cookie="xmlink_gate=v1; Max-Age=2592000; Path=/; Secure; SameSite=None"</script>
3444</body>
3445</html>

Line numbers count LF bytes from the start of the resource, as the search results do. Vendor segments are library code the classifier recognised; they are stored but not indexed. Bytes are shown as Latin1 characters, one per byte.