Lactobacillus johnsonii mediates the protective effects of pristimerin against ulcerative colitis and concomitant liver injury through remodeling hepatic lipid metabolism via LXRα-SCD1 axis.

Authors

Yan Cheng, Zhanxuan E Wu, Ruoyue Huang, Qingmei Li, Dongmei Yan, Yuqi Chen, WeiFeng Zhu, Fei Li

Published in

Gut microbes. Volume 18. Issue 1. Pages 2701349. Dec 31, 2026. Epub Jul 17, 2026.

Abstract

Ulcerative colitis (UC) is a systemic disease that can involve multiple organs, and hepatobiliary diseases in UC patients are frequently observed. However, the pathogenesis of UC and its associated hepatobiliary complications remains elusive, and limited therapeutic options are available. This study revealed that disrupted hepatic lipid metabolism plays a pivotal role in driving the progression of UC and its extraintestinal hepatobiliary manifestations. Mechanistically, colitis-elevated circulating endogenous corticosterone (CORT) mediates the downregulation of hepatic LXRα-SCD1 signaling, resulting in diminished monounsaturated fatty acid (MUFA), reduced unsaturated lysophospholipids, and the accumulation of alkyl lysophospholipids, ceramide and hexosylceramide. These alterations contribute to liver lipotoxicity and, in turn, exacerbate colitis. A similar lipid profile is observed in UC patients. Importantly, pristimerin, a natural compound structurally similar to the star molecule celastrol, has been demonstrated to alleviate UC and concomitant liver injury by remodeling hepatic lipid metabolism in a microbiota-dependent manner. The gut commensal Lactobacillus johnsonii mediates the effects of PSM by activating hepatic LXRα-SCD1 signaling and increasing the potential anti-inflammation lipid species LPC20:2 and LPC20:3. This investigation suggests a novel therapeutic strategy for UC and associated liver injury based on the L. johnsonii-hepatic LXRα-SCD1 axis. This study also opens new avenues for mechanistic exploration of systemic diseases and therapeutic strategies of multi-organ comorbidity.

PMID:
42470108
Bibliographic data and abstract were imported from PubMed on 18 Jul 2026.

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