ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Microbial Physiology and Metabolism
This article is part of the Research TopicRecent Advances in Biotechnological Applications of Microbial Secondary Metabolites, Vol IIView all articles
The metabolite ILA of Akkermansia muciniphila improves AP-related intestinal injury by targeting and inhibiting CASP3 activity
Provisionally accepted
- 1The First Affiliated Hospital of Jinan University, Guangzhou, China
- 2Department of critical care medicine, The First People's Hospital of Chenzhou, The ChenZhou Affiliated Hospital, Hengyang Medical School, University of South China, Chenzhou, Hunan, China
- 3The First People's Hospital of Chenzhou, Chenzhou, China
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Objective: 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. Akkermansia muciniphila (AKK) is recognised 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. Design: 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. Results: 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. Conclusion: 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.
Keywords: ILA, gut microbiome, acute pancreatitis, Intestinal injury, CASP3
Received: 19 Jul 2025; Accepted: 10 Nov 2025.
Copyright: © 2025 Li, Yu, Li, Dai and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Zhiwang Li, lizhiwanghn@163.com
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