{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T22:40:08Z","timestamp":1793400008280,"version":"4.5.0"},"reference-count":192,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiomes"],"abstract":"<jats:p>Fecal microbiota transplantation (FMT) has evolved from an empirical remedy for recurrent Clostridioides difficile infection (rCDI) into a foundational platform for precision microbiome-based therapeutics. This comprehensive review details FMT\u2019s journey, analyzing its multifaceted mechanisms of action\u2014including restoration of colonization resistance, metabolic reprogramming via short-chain fatty acids and bile acids, and profound immunomodulation\u2014which extend far beyond simple microbial replacement. We critically evaluate its established, high efficacy in rCDI and its expanding, albeit more variable, applications across a wide spectrum of gastrointestinal diseases (such as inflammatory bowel disease, irritable bowel syndrome, and constipation), neurological disorders (including Parkinson\u2019s and Alzheimer\u2019s disease), metabolic conditions, autoimmune diseases, and oncology (particularly in modulating response to immune checkpoint inhibitors and treating graft-versus-host disease). The review further discusses the critical challenges of donor-recipient variability, safety, and the lack of standardized protocols that have driven the field\u2019s technical evolution. This progression encompasses refined processing methods like washed microbiota transplantation (WMT), diverse delivery routes including oral capsules, and the exploration of non-bacterial components like bacteriophages through fecal filtrate transplantation (FVT). Ultimately, we highlight the field\u2019s trajectory toward next-generation, defined live biotherapeutic products (LBPs) and engineered microbial consortia, aiming to transition from the complex \u201cblack box\u201d of whole stool to safer, more consistent, and rationally designed precision therapies that target the specific dysbiotic networks underlying diverse human diseases.<\/jats:p>","DOI":"10.3389\/frmbi.2026.1863308","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T05:57:07Z","timestamp":1781675827000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Fecal microbiota transplantation: from empirical remedy to precision medicine"],"prefix":"10.3389","volume":"5","author":[{"given":"Junsheng","family":"Zhao","sequence":"first","affiliation":[{"name":"Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan (Hangzhou) Hospital Affiliated to Shulan International Medical College, Zhejiang Shuren University","place":["Hangzhou, China"]},{"name":"State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiming","family":"Fan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan (Hangzhou) Hospital Affiliated to Shulan International Medical College, Zhejiang Shuren University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keda","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan (Hangzhou) Hospital Affiliated to Shulan International Medical College, Zhejiang Shuren University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hainv","family":"Gao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan (Hangzhou) Hospital Affiliated to Shulan International Medical College, Zhejiang Shuren University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1602","DOI":"10.1093\/cid\/ciac207","article-title":"Cost-effectiveness of fecal microbiota transplantation for first recurrent Clostridioides difficile infection","volume":"75","author":"Aby","year":"2022","journal-title":"Clin. 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