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Inflammation Research
Published in: Inflammation Research 10-11/2022

17-09-2022 | Respiratory Microbiota | Original Research Paper

Synergistic anti-inflammatory effect of gut microbiota and lithocholic acid on liver fibrosis

Authors: Junwei Shao, Tiantian Ge, Cuilan Tang, Gang Wang, Lantian Pang, Zhi Chen

Published in: Inflammation Research | Issue 10-11/2022

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Abstract

Background

Bile acids can regulate liver disease progression by affecting the functions of gut microbiota and immune cells. As the most potent natural agonist of G-protein coupled bile acid receptor 5 (TGR5) (expressed in macrophages, HSCs, and monocytes), lithocholic acid (LCA) has multiple functions, such as inhibiting inflammation and regulating metabolism. Therefore, this study aims to investigate the effects of LCA on immune cells and HSCs in liver fibrosis.

Methods

A liver fibrosis mouse model was induced by carbon tetrachloride followed by gavage of LCA, and the effects of LCA were evaluated by serum biochemical analysis, liver histology, and western bolt. Plasma cytokine levels and the number of immune cells were determined by cytometric bead array and flow cytometry, respectively.

Results

LCA could inhibit the activation of HSCs by inducing apoptosis and reducing the activation of transforming growth factor-β (TGF-β) Smad-dependent and Smad-independent pathways. Meanwhile, LCA inhibited glycolysis and promoted oxidative phosphorylation, leading to the differentiation of macrophages to M2 type and inhibiting their differentiation to M1 type. Furthermore, LCA increased the recruitment of NK cells and reduced the activation of NKT cells. However, these effects of LCA were attenuated after antibiotics reduced the diversity and abundance of the gut microbiota.

Conclusions

Gut microbiota and LCA exerted synergistic anti-inflammatory effects on liver fibrosis. The combined intervention of gut microbiota and LCA will be a new strategy for treating liver fibrosis.
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Metadata
Title
Synergistic anti-inflammatory effect of gut microbiota and lithocholic acid on liver fibrosis
Authors
Junwei Shao
Tiantian Ge
Cuilan Tang
Gang Wang
Lantian Pang
Zhi Chen
Publication date
17-09-2022
Publisher
Springer International Publishing
Published in
Inflammation Research / Issue 10-11/2022
Print ISSN: 1023-3830
Electronic ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-022-01629-4

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