Clostridium sporogenes increases fat accumulation in mice by enhancing energy absorption and adipogenesis

ABSTRACT Gut bacteria belonging to the Clostridium family play a pivotal role in regulating host energy balance and metabolic homeostasis. As a commensal bacterium, Clostridium sporogenes has been implicated in modulating host energy homeostasis, albeit the underlying mechanism remains elusive. Therefore, this study aimed to investigate the impact of C. sporogenes supplementation on various physiological parameters, intestinal morphology, particularly adipose tissue accumulation, and glucolipid metabolism in mice. The findings reveal that mice supplemented with C. sporogenes for 6 weeks exhibited a notable increase in body weight, fat mass, adipocyte size, and serum triglyceride (TG) levels. Notably, the increased fat accumulation is observed despite consistent feed intake in treated mice. Mechanistically, C. sporogenes supplementation significantly improved the structure integrity of intestinal villi and enhanced energy absorption efficiency while reducing excretion of carbohydrates and fatty acids in feces. This was accompanied by upregulation of glucose and fatty acid transporter expression. Furthermore, supplementation with C. sporogenes promoted adipogenesis in both liver and adipose tissues, as evidenced by increased levels of hepatic pyruvate, acetyl-CoA, and TG, along with elevated expression levels of genes associated with lipid synthesis. Regarding the microbiological aspect, C. sporogenes supplementation correlated with an increased abundance of Clostridium genus bacteria and enhanced carbohydrate enzyme activity. In summary, C. sporogenes supplementation significantly promotes fat accumulation in mice by augmenting energy absorption and adipogenesis, possibly mediated by the expansion of Clostridium bacteria population with robust glycolipid metabolic ability. IMPORTANCE The Clostridia clusters have been implicated in energy metabolism, the specific species and underlying mechanisms remain unclear. This present study is the first to report Clostridium sporogenes is able to affect fat accumulation and glycolipid metabolism. We indicated that gavage of C. sporogenes promoted the adipogenesis and fat accumulation in mice by not only increasing the abundance of Clostridium bacteria but by also enhancing the metabolic absorption of carbohydrates and fatty acids significantly. Obviously, changes of gut microbiota caused by the C. sporogenes , especially the significant increase of Clostridium bacteria, contributed to the fat accumulation of mice. In addition, the enhancement of Clostridium genus bacteria remarkably improved the synthesis of hepatic pyruvate, acetyl-CoA, and triglyceride levels, as well as reduced the excretion of fecal carbohydrates, short-chain fatty acids, and free fatty acids remarkably. These findings will help us to understand the relationship of specific bacteria and host energy homeostasis.