State Key Laboratory of Microbial Technology, Shandong University, Qingdao, P. R. China.
State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, P. R. China.
Nat Microbiol. 2024 Feb;9(2):434-450. doi: 10.1038/s41564-023-01570-0. Epub 2024 Jan 17.
A strong correlation between gut microbes and host health has been observed in numerous gut metagenomic cohort studies. However, the underlying mechanisms governing host-microbe interactions in the gut remain largely unknown. Here we report that the gut commensal Christensenella minuta modulates host metabolism by generating a previously undescribed class of secondary bile acids with 3-O-acylation substitution that inhibit the intestinal farnesoid X receptor. Administration of C. minuta alleviated features of metabolic disease in high fat diet-induced obese mice associated with a significant increase in these acylated bile acids, which we refer to as 3-O-acyl-cholic acids. Specific knockout of intestinal farnesoid X receptor in mice counteracted the beneficial effects observed in their wild-type counterparts. Finally, we showed that 3-O-acyl-CAs were prevalent in healthy humans but significantly depleted in patients with type 2 diabetes. Our findings indicate a role for C. minuta and acylated bile acids in metabolic diseases.
在许多肠道宏基因组队列研究中，都观察到肠道微生物与宿主健康之间存在很强的相关性。然而，肠道中支配宿主-微生物相互作用的潜在机制在很大程度上仍是未知的。在这里，我们报告肠道共生菌 Christensenella minuta 通过生成一类具有 3-O 酰化取代的以前未被描述的次级胆汁酸来调节宿主代谢，该胆汁酸可抑制肠道法尼醇 X 受体。C. minuta 的给药缓解了高脂肪饮食诱导的肥胖小鼠的代谢疾病特征，与这些酰化胆汁酸的显著增加相关，我们将其称为 3-O-酰基胆酸。在小鼠中特异性敲除肠道法尼醇 X 受体，抵消了在其野生型对应物中观察到的有益作用。最后，我们表明 3-O-酰基-CAs 在健康人群中普遍存在，但在 2 型糖尿病患者中明显减少。我们的研究结果表明 C. minuta 和酰化胆汁酸在代谢性疾病中发挥作用。
