Inflammation research : official journal of the European Histamine Research Society ... [et al.]Sep 17, 2022

Combined anti-inflammatory effects of gut bacteria and lithocholic acid on liver scarring

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 31, 2026

Abstract

Lithocholic acid (LCA) inhibited the activation of hepatic stellate cells (HSCs) through apoptosis and modulation of specific signaling pathways.

LCA may reduce the activation of TGF-β signaling pathways associated with liver fibrosis.
LCA is linked to enhanced differentiation of macrophages into an anti-inflammatory M2 type while inhibiting the pro-inflammatory M1 type.
The recruitment of natural killer (NK) cells increased with LCA treatment, alongside a reduction in the activation of NKT cells.
The beneficial effects of LCA were diminished when antibiotics were used, which lowered the diversity and abundance of gut microbiota.
Gut microbiota and LCA may work together to provide anti-inflammatory effects in liver fibrosis.

Simplified

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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Combined anti-inflammatory effects of gut bacteria and lithocholic acid on liver scarring

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