The gut microbe Bacteroides acidifaciens ameliorates CCl4-induced liver fibrosis.

BACKGROUND & AIMS: Liver fibrosis is an inevitable outcome of various manifestations of progressive chronic liver disease. Clinical evidence suggests that gut microbiota contributes to the progression of liver fibrosis via gut-liver axis. Our previous research demonstrated that GL-V9, one of flavonoids compounds, is effective in alleviating liver fibrosis in mice. Based on that, we decided to delve into the alterations in gut microbiota profiling of GL-V9-treated mice with liver fibrosis and identify the bacterial species exhibiting anti-fibrotic potential.

METHODS

We explored gut microbial profile of GL-V9-treated mice with liver fibrosis via 16S rRNA gene sequencing. Mouse models of liver fibrosis were established and treated accordingly. Then, indexes of liver fibrosis and inflammation were measured by sections staining, biochemical detection and RT-qPCR. Regulatory T (Treg) cells infiltration was detected by flow cytometry. Furthermore, we detected short-chain fatty acids (SCFAs) content by GC-MS and explored the role of SCFAs in liver fibrosis.

RESULTS

Firstly, Bacteroides acidifaciens were screened out by 16S rRNA gene sequencing based on GL-V9 treatment. Oral administration of Bacteroides acidifaciens attenuated CCl4-induced liver fibrosis effectively, reduced the expressions of pro-inflammatory factor and suppressed the infiltration of Treg cells. Additionally, SCFAs, the main metabolites of Bacteroides acidifaciens, were further demonstrated the suppression of fibrosis and inflammation. Mechanistically, Bacteroides acidifaciens regulated SCFAs metabolic homeostasis and subsequently inhibited Treg cells infiltration via regulating PI3K/AKT/mTOR pathway.

CONCLUSIONS

In CCl4-induced liver fibrosis mice, Bacteroides acidifaciens and its derived SCFAs exhibit excellent anti-fibrosis effects, which provides a new strategy for liver fibrosis treatment.