Gut Microbiota‐Butyrate‐PPARγ Axis Modulates Adipose Regulatory T Cell Population

Abstract Gut microbiota is essential for the function of peripherally‐induced regulatory T (pTreg) cells. However, how commensal bacteria affect thymically derived fat‐resident Treg cells that harbor a unique expression of peroxisome proliferator‐activated receptor (PPAR)‐γ and suppress inflammation in visceral adipose tissue (VAT), is not well defined. Here it is revealed that microbiota depletion causes a drastic decline in Treg cell population in VAT, particularly those expressing ST2 (ST2 + Treg), which are largely restored after gut microbiome reconstruction. Mechanistically, gut microbiota‐derived butyrate increases VAT ST2 + Treg cells through binding PPARγ. Butyrate supplementation and high fiber diet increase VAT ST2 + Treg population in obese mice, and ameliorated glucose tolerance and visceral inflammation. Furthermore, human omental adipose Treg cells show positive correlation with fecal butyrate and certain butyrate‐producing microbes. This study identifies the critical role of gut microbiota‐butyrate‐PPARγ axis in maintaining VAT Treg population, pinpointing a potential approach to augment VAT Treg population and ameliorate inflammation.