{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T11:06:00Z","timestamp":1789988760584,"version":"4.0.1"},"reference-count":163,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82670700"],"award-info":[{"award-number":["82670700"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82100549"],"award-info":[{"award-number":["82100549"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82670700"],"award-info":[{"award-number":["82670700"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["82100549"],"award-info":[{"award-number":["82100549"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Natural Science Foundation of Guangdong province, China","award":["2025A1515010070"],"award-info":[{"award-number":["2025A1515010070"]}]},{"name":"\u201cDengfeng Plan\u201d Fund of the First Affiliated Hospital, Sun Yat-sen University","award":["R70001"],"award-info":[{"award-number":["R70001"]}]},{"name":"\u201cKe Lin Young Talent\u201d Fund of the First Affiliated Hospital, Sun Yat-sen University","award":["R07010"],"award-info":[{"award-number":["R07010"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Inflammatory bowel disease (IBD), encompassing Crohn\u2019s disease (CD) and ulcerative colitis (UC), is a chronic relapsing intestinal inflammatory disorder driven by complex interactions among host genetics, immune dysregulation, and gut microbiota dysbiosis. The functional contribution of microbial metabolites beyond short-chain fatty acids and bile acids remains incompletely understood. A critical and unresolved question is whether microbiota-associated amino acid metabolites are merely passive indicators of dysbiosis or active drivers of intestinal inflammation and tissue repair. In this review, we summarize recent advances in the roles of microbiota-associated amino acid metabolites and their derivatives in IBD, highlighting that amino acid metabolites constitute a functionally distinct class of bioactive signaling molecules that operate through four representative metabolic networks: tryptophan metabolism, aspartate-related metabolism, branched-chain amino acid (BCAA) metabolism, and arginine\u2013polyamine metabolism. We synthesize recent clinical metabolomic data and identify reductions in tryptophan-derived indoles, glutamate, histidine, and selected BCAAs across IBD clinical cohorts and sample matrices, whereas metabolites such as serine, proline, and polyamine degradation products are frequently elevated or associated with disease activity or therapeutic response. Mechanistically, microbiota-associated amino acid metabolites are implicated in intestinal homeostasis and IBD pathogenesis through multifaceted pathways, including modulation of intestinal epithelial barrier integrity (e.g., cell\u2013cell junction, mucus secretion, and stem cell-driven mucosal repair), innate and adaptive immune responses, host\u2013pathogen interactions, and extraintestinal inflammatory signaling (e.g., systemic inflammation, and brain\u2013gut axis communication). Finally, we highlight current challenges and limitations in achieving a causal understanding of microbiota-associated amino acid metabolic alterations in IBD, particularly regarding their origin, spatial distribution, and functional relevance, as well as their potential utility for disease stratification and treatment-response assessment, and discuss how these insights may inform the future development of next-generation biomarkers and precision therapeutic strategies tailored to individual metabolic phenotypes in IBD.<\/jats:p>","DOI":"10.3390\/microorganisms14092108","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T10:25:43Z","timestamp":1789986343000},"page":"2108","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Microbiota-Associated Amino Acid Metabolites in Inflammatory Bowel Disease: Emerging Key Players in the Host\u2013Microbe Interface"],"prefix":"10.3390","volume":"14","author":[{"given":"Xianwen","family":"Meng","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7923-7381","authenticated-orcid":false,"given":"Chunyang","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijun","family":"Zhu","sequence":"additional","affiliation":[{"name":"Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0315-1723","authenticated-orcid":false,"given":"Danping","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1016\/S0140-6736(23)02586-2","article-title":"Crohn\u2019s disease","volume":"403","author":"Dolinger","year":"2024","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/S0140-6736(23)00966-2","article-title":"Ulcerative colitis","volume":"402","author":"Honap","year":"2023","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2769","DOI":"10.1016\/S0140-6736(17)32448-0","article-title":"Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: A systematic review of population-based studies","volume":"390","author":"Ng","year":"2017","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1053\/j.gastro.2021.12.282","article-title":"Twenty-first century trends in the global epidemiology of pediatric-onset inflammatory bowel disease: Systematic review","volume":"162","author":"Kuenzig","year":"2022","journal-title":"Gastroenterology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e0021024","DOI":"10.1128\/cmr.00210-24","article-title":"Narrative review on bacteria-derived metabolites in the pathogenesis of ulcerative colitis","volume":"38","author":"Tambovtseva","year":"2025","journal-title":"Clin. 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