{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T20:12:37Z","timestamp":1793045557049,"version":"4.5.0"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hunan Provincial Education Department"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Acute Pancreatitis (AP) is a common acute abdominal disease in clinical practice. The gut microbiome is recognized as a key regulator in the development of acute pancreatitis.\n                      <jats:italic>Akkermansia muciniphila<\/jats:italic>\n                      (AKK) is recognized as a functional probiotic strain and has a beneficial effect on the progression of many diseases. However, the role of the AKK in the development of AP remains unclear. Here, we evaluated the potential contribution of AKK to AP.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Relative abundance of gut microbial AKK in AP was evaluated. A rat model of acute pancreatitis was established by retrograde pancreatic duct infusion of sodium taurocholate. Non-targeted and targeted metabolomics analysis were used for metabolites analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We first found that the relative abundance of gut microbial AKK in AP patients was significantly reduced compared with that in healthy subjects. Live AKK supplementation, as well as supplementation with its culture supernatant, remarkably alleviates AP-related intestinal injury in AP rat models. Metabolomics studies found that the live AKK was able to generate Indole-3-lactic acid (ILA). ILA exerted a protective effect against AP-related intestinal injury, and significantly reduce inflammatory cell activation and pro-inflammatory factor overproduction. The mechanistic study revealed that ILA inhibits the apoptosis of intestinal epithelial cells by suppressing the activity of CASP3, and improves the role of intestinal barrier dysfunction in the AP model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We revealed that ILA, derived from live AKK, may act as a novel endogenous agonist for CASP3. ILA may serve as a new potential treatment method for intestinal injury in AP after successfully translating its efficacy into clinical practice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2025.1669383","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T11:29:22Z","timestamp":1764934162000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["The metabolite ILA of Akkermansia muciniphila improves AP-related intestinal injury by targeting and inhibiting CASP3 activity"],"prefix":"10.3389","volume":"16","author":[{"given":"Peiyu","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiuliang","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyong","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuqi","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyang","family":"Guan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiming","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingui","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,5]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1016\/j.molmed.2016.04.003","article-title":"Antibiotic-induced changes in the intestinal microbiota and disease","volume":"22","author":"Becattini","year":"2016","journal-title":"Trends Mol. Med."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"11422","DOI":"10.3390\/ijms231911422","article-title":"Functional plasmon-activated water increases Akkermansia muciniphila abundance in gut microbiota to ameliorate inflammatory bowel disease","volume":"23","author":"Chang","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"833","DOI":"10.3390\/toxins14120833","article-title":"MC-LR aggravates liver lipid metabolism disorders in obese mice fed a high-fat diet via PI3K\/AKT\/mTOR\/SREBP1 signaling pathway","volume":"14","author":"Chu","year":"2022","journal-title":"Toxins (Basel)."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"7767","DOI":"10.1128\/AEM.01477-07","article-title":"Intestinal integrity and Akkermansia muciniphila, a mucin-degrading member of the intestinal microbiota present in infants, adults, and the elderly","volume":"73","author":"Collado","year":"2007","journal-title":"Appl. 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Med."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/s41421-025-00789-x","article-title":"A decrease in Flavonifractor plautii and its product, phytosphingosine, predisposes individuals with phlegm-dampness constitution to metabolic disorders","volume":"11","author":"Li","year":"2025","journal-title":"Cell Discov."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1080\/14740338.2024.2396387","article-title":"Clinical features, treatment, and prognosis of SGLT2 inhibitors induced acute pancreatitis","author":"Li","year":"2025","journal-title":"Expert Opin. Drug Saf."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.1007\/s12602-023-10101-6","article-title":"Akkermansia muciniphila protects against antibiotic-associated diarrhea in mice","volume":"16","author":"Liu","year":"2024","journal-title":"Probiotics Antimicrob Proteins"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/j.ccc.2015.12.006","article-title":"Severe acute pancreatitis and necrotizing pancreatitis","volume":"32","author":"Maheshwari","year":"2016","journal-title":"Crit. Care Clin."},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2020.1870402","article-title":"Association between antibiotics and gut microbiome dysbiosis in children: systematic review and meta-analysis","volume":"13","author":"McDonnell","year":"2021","journal-title":"Gut Microbes"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"e01014\u2013e01017","DOI":"10.1128\/aem.01014-17","article-title":"Genome-scale model and omics analysis of metabolic capacities of Akkermansia muciniphila reveal a preferential mucin-degrading lifestyle","volume":"83","author":"Ottman","year":"2017","journal-title":"Appl. Environ. Microbiol."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"e3000410","DOI":"10.1371\/journal.pbio.3000410","article-title":"The ARRIVE guidelines 2.0: updated guidelines for reporting animal research","volume":"18","author":"Percie du Sert","year":"2020","journal-title":"PLoS Biol."},{"key":"ref17","first-page":"138","article-title":"Intestinal permeability and systemic endotoxemia in patients with acute pancreatitis","volume":"87","author":"Schietroma","year":"2016","journal-title":"Ann. Ital. Chir."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1097\/00000658-199201000-00007","article-title":"A better model of acute pancreatitis for evaluating therapy","volume":"215","author":"Schmidt","year":"1992","journal-title":"Ann. Surg."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.1007\/s40265-022-01766-4","article-title":"Acute pancreatitis: diagnosis and treatment","volume":"82","author":"Szatmary","year":"2022","journal-title":"Drugs"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"e70048","DOI":"10.1002\/imt2.70048","article-title":"Gut microbiota-derived butyric acid regulates calcific aortic valve disease pathogenesis by modulating GAPDH lactylation and butyrylation","volume":"4","author":"Wang","year":"2025","journal-title":"iMeta"},{"key":"ref21","volume-title":"Front Microbiol","author":"Wu","year":""},{"key":"ref22","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1136\/gutjnl-2023-329996","article-title":"Novel tripeptide RKH derived from Akkermansia muciniphila protects against lethal sepsis","volume":"73","author":"Xie","year":"2023","journal-title":"Gut"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"2924","DOI":"10.1038\/s41598-025-86664-x","article-title":"Clinical significance of PCT, CRP, IL-6, NLR, and TyG index in early diagnosis and severity assessment of acute pancreatitis: a retrospective analysis","volume":"15","author":"Xinyu","year":"2025","journal-title":"Sci Rep."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"194","DOI":"10.3390\/metabo13020194","article-title":"Akkermansia muciniphila alleviates persistent inflammation, immunosuppression, and catabolism syndrome in mice","volume":"13","author":"Xu","year":"2023","journal-title":"Meta"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"3227","DOI":"10.1080\/10408398.2018.1517725","article-title":"A next generation probiotic, Akkermansia muciniphila","volume":"59","author":"Zhai","year":"2019","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref26","doi-asserted-by":"crossref","first-page":"59","DOI":"10.3390\/biom14010059","article-title":"The interaction of microbiome and pancreas in acute pancreatitis","volume":"14","author":"Zhang","year":"2023","journal-title":"Biomolecules"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"2100536","DOI":"10.1002\/advs.202100536","article-title":"Decreased abundance of Akkermansia muciniphila leads to the impairment of insulin secretion and glucose homeostasis in lean type 2 diabetes","volume":"8","author":"Zhang","year":"2021","journal-title":"Adv. Sci."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"2375555","DOI":"10.1080\/21505594.2024.2375555","article-title":"Akkermansia muciniphila: a promising probiotic against inflammation and metabolic disorders","volume":"15","author":"Zhao","year":"2024","journal-title":"Virulence"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1016\/j.jinf.2019.10.008","article-title":"The effect of antibiotics on the composition of the intestinal microbiota - a systematic review","volume":"79","author":"Zimmermann","year":"2019","journal-title":"J. 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