Multi-omics reveals deoxycholic acid modulates bile acid metabolism via the gut microbiota to antagonize carbon tetrachloride-induced chronic liver injury

ABSTRACT

Deoxycholic acid (DCA) serves essential functions in both physiological and pathological liver processes; nevertheless, the relationship among DCA, gut microbiota, and metabolism in chronic liver injury remain insufficiently understood. The primary objective of this study is to elucidate the potential of DCA in ameliorating chronic liver injury and evaluate its regulatory effect on gut microbiota and metabolism via a comprehensive multi-omics approach. Our study found that DCA supplementation caused significant changes in the composition of gut microbiota, which were essential for its antagonistic effect against CCl₄-induced chronic liver injury. When gut microbiota was depleted with antibiotics, the observed protective efficacy of DCA against chronic liver injury became noticeably attenuated. Mechanistically, we discovered that DCA regulates the metabolism of bile acids (BAs), including 3-epi DCA, Apo-CA, and its isomers 12-KLCA and 7-KLCA, IHDCA, and DCA, by promoting the growth of A.muciniphila in gut microbiota. This might lead to the inhibition of the IL-17 and TNF inflammatory signaling pathway, thereby effectively countering CCl₄-induced chronic liver injury. This study illustrates that the enrichment of A. muciniphila in the gut microbiota, mediated by DCA, enhances the production of secondary bile acids, thereby mitigating chronic liver injury induced by CCl₄. The underlying mechanism may involve the inhibition of hepatic IL-17 and TNF signaling pathways. These findings propose a promising approach to alleviate chronic liver injury by modulating both the gut microbiota and bile acids metabolism.

KEYWORDS:

• Chronic liver injury
• gut microbiota
• metabolism
• transcriptome
• inflammation
• deoxycholic acid

Acknowledgments

The authors thank all the participants in this study for their cooperation in sample preparation.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Authors’ contributions

YZ and QO conceived the concept of the project; LZ and YZ designed the studies; TC, CL, and YZ, collected the samples and clinical information; LZ, ZZ, and HH performed experiments. LZ, YF, and TC performed initial data analysis; LZ, ZZ and QY performed the final analysis of the data; LZ, YZ and wrote the manuscript. YZ, CL and QO revised the manuscript. All authors reviewed the manuscript.

Data availability statement

The datasets that support the findings of the study are available from the corresponding author upon reasonable request. The 16S rRNA gene sequencing data from this study are available in the NCBI Sequence Read Archive (SRA) repository under the accession number PRJNA1031407.

Ethics approval and consent to participate

The study was approved by the Ethics Committee of the First Affiliated Hospital of Fujian Medical University (MTCA, ECFAH of FMU [2021] 047). Written informed consent was obtained from each patient. Animal experiments were approved by the Animal Ethics Committee of Fujian Medical University (IACUC FJMU 2021–0307).

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2024.2323236

Additional information

Funding

The study is supported by grants from National Natural Science Foundation of China (Grant numbers 82172338, 82202596, 82372316).