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

delete2026-07-17
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OA
AI
Y
Yan Cheng
Z
Zhanxuan E. Wu
R
Ruoyue Huang
Q
Qingmei Li
许文波 (Wenbo Xu)
Y
Yuqi Chen
W
WeiFeng Zhu *
F
Fei Li *
DOI:10.1080/19490976.2026.2701349delete
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Abstract

Abstract

En 中文
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.
Keywords:
Lactobacillus johnsonii
pristimerin
ulcerative colitis
liver injury
gut–liver axis

Journal

Gut Microbes cover
Gut Microbes
IF:
11
Papers:
2.7K
Citations:
1.9W

Organization

S
sichuan university
Scholars:
11.5W
Papers: 7.6W
Citations: 100
J
jiangxi university of chinese medicine
Scholars:
414
Papers: 116
Citations: 0
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