With the change of modern lifestyle and the prevalence of high-fat and high-sugar diets, the incidence of metabolic diseases has been steadily increasing. The gut microbiota participates in host metabolism and is closely linked to the development and prevention of metabolic diseases. Therefore, exploring and deciphering the functions and mechanisms of gut microbes hold promise for the development of new therapeutic strategies for chronic metabolic diseases.On January 17, 2024, the research group from the Institute of Microbiology, Chinese Academy of Sciences and Shandong University jointly published a study in Nature Microbiology titled "Gut commensal Christensenella minuta modulates host metabolism via acylated secondary bile acids." This research unveils a novel mechanism through which gut commensal microbes, represented by Christensenella minuta, alleviate metabolic disorders in the host by producing a new class of secondary bile named as 3-O-acyl-cholic acids. The work highlights the promising applications of Christensenella minuta and acylated bile acids for the treatment and prevention of metabolic disorders, including Type 2 diabetes.
The study revealed that gut commensal microbes represented by Christensenella minuta modulate host metabolism by generating a novel class of acylated bile acids that inhibit the intestinal farnesoid X receptor (FXR). By profiling 88 gut microbial species negatively associated with metabolic diseases on the transformation activity against cholic acid, nine gut commensals including Christensenella minuta were characterized to produce a class of novel secondary bile acids with 3-O-acylation substitution. Subsequently, administration of Christensenella minuta alleviated metabolic disorders in high-fat-diet-induced obese mice, which is parallel with a significant increase of 3-O-acyl-cholic acids and targeted regulation of intestinal FXR-enterohepatic signalling axes. Specific knockout of intestinal FXR in mice counteracted the beneficial effects observed in their wild-type counterparts. Finally, it was showed that 3-O-acyl-cholic acids were widely distributed in healthy humans but significantly depleted in patients with type 2 diabetes in a cohort study. This research underscores the potential of Christensenella minuta and acylated bile acids in the treatment and prevention of metabolic diseases.
This work was supported by the National Key Research and Development Program of China, and the National Science Fund for Distinguished Young Scholars. The corresponding authors are Prof. LIU Shuangjiang from the Institute of Microbiology, Chinese Academy of Sciences/Shandong University, Prof. LIU Hongwei from Institute of Microbiology, Chinese Academy of Sciences, and Professor JIANG Changtao from Peking University.
Figure: Diagram Illustrating the Mechanism of Christensenella minuta-Mediated Alleviation of Hyperglycemia and Hyperlipidemia. (Image by Prof. Liu Shuangjiang’s group)
Contact:
LIU Shuangjiang
Institute of Microbiology, Chinese Academy of Sciences
Phone: 86-010-64807423
E-mail: liusj@im.ac.cn
Research
