ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Microbial Symbioses
This article is part of the Research TopicExploring Novel Mechanisms of Microbial Symbiosis in Robust Environmental SystemsView all 3 articles
Akkermansia muciniphila alleviates antibiotic-and LPS-induced oxidative stress via the p38α MAPK–Nrf2 signaling axis
Provisionally accepted
Wen-Yu Ye1,2
Cai-Xia Feng1,2
Shi-Qi Su1,2Su-Mei Wei1,2Ying Mao1,2Zhen-Yu Chen1,2Ying Su1,2Qing-Wen Shan1,2*- 1The First Affiliated Hospital of Guangxi Medical University, Nanning, China
- 2Difficult and Critical illness Center, Pediatric Clinical Medical Research Center of Guangxi, Nanning, China
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Antibiotic abuse and subsequent infection induce dysregulation of the intestinal epithelial kinome, characterized by p38α hyperphosphorylation (encoded by MAPK14), serving as a common molecular trigger for barrier failure. However, readily druggable nodes to repair this dysregulation remain elusive. In an antibiotic-LPS co-exposure enteropathy model, we found that Akkermansia muciniphila (AKK) reactivates the "p38α MAPK–Nrf2" signaling pathway. Mechanistically, AKK specifically alleviates p38α subtype-mediated suppression of Nrf2, thereby synergistically enhancing the expression of antioxidant enzymes such as HO-1 and NQO1, reducing excessive reactive oxygen species (ROS) production, and restoring the integrity of epithelial tight junctions and mucus layers. Our work is the first to establish the "AKK–p38α MAPK–Nrf2" axis as a druggable kinase module for antibiotic-associated intestinal disease, providing an immediately translatable molecular foundation for developing oral, mechanism-defined, and precise microecological therapies.
Keywords: Akkermansia muciniphila, Antibiotic-associated enteropathy, intestinal barrier function, Nrf2 signaling, p38α MAPK
Received: 27 Nov 2025; Accepted: 15 Jan 2026.
Copyright: © 2026 Ye, Feng, Su, Wei, Mao, Chen, Su and Shan. 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: Qing-Wen Shan
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