Glycoursodeoxycholic acid regulates bile acids level and alters gut microbiota and glycolipid metabolism to attenuate diabetes

ABSTRACT

Accumulating evidence suggests that the bile acid regulates type 2 diabetes mellitus (T2DM) through gut microbiota-host interactions. However, the mechanisms underlying such interactions have been unclear. Here, we found that glycoursodeoxycholic acid (GUDCA) positively regulates gut microbiota by altering bile acid metabolism. GUDCA in mice resulted in higher taurolithocholic acid (TLCA) level and Bacteroides vulgatus abundance. Together, these changes resulted in the activation of the adipose G-protein-coupled bile acid receptor, GPBAR1 (TGR5) and upregulated expression of uncoupling protein UCP-1, resulting in elevation of white adipose tissue thermogenesis. The anti-T2DM effects of GUDCA are linked with the regulation of the bile acid and gut microbiota composition. This study suggests that altering bile acid metabolism, modifying the gut microbiota may be of value for the treatment of T2DM.

KEYWORDS:

• Type 2 diabetes
• bile acids
• gut microbiota
• glycoursodeoxycholic acid

Acknowledgments

We appreciate the technical assistance for the operation of MiSeq and UPLC-MS/MS from Shanghai Biotree Biological Technology Co., Ltd. (Shanghai, China).

Disclosure statement

No potential conflict of interest was reported by the authors.

Author contributions

M-X.L. conceived and designed the research. C-B.T. and B.Y. performed the experiments and the statistical analyses. T-F.L. and Y-J.L. helped with the animal experiments and analyzed the data. Z.R. and Z-Y.W. helped with the SCFA analysis experiments and revised the manuscript. T-H.W. helped with the WB experiments.

Data availability statement

The data that support the findings of this study are available in https://www.ncbi.nlm.nih.gov/bioproject/PRJNA855315, reference number PRJNA855315, and within the article and its supplementary materials.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2023.2192155.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (no.81760753), Major Scientific and Technological Project of the Xinjiang Uygur Autonomous Region (no.2022A03007-3) and the University Research Program of China (XJEDUY026).