Calorie-restricted diet reshapes gut microbiota to alleviate obesity potentially via SCFAs-UCP2-AMPK signaling pathway

Alterations of gut microbial community structure and its related metabolic disorders are key factors causing obesity. However, the interactive mechanism between calorie-restricted diet reducing obesity and gut microbial homeostasis has yet to be fully clarified. This study enrolled a cohort of Chinese obese patients for a 3-month CRD intervention and used fecal microbiota transplantation with analyzing the gut microbiota to investigate the ameliorative effects of CRD on obesity. We found that CRD intervention significantly reduced body weight and altered the gut microbial structure based on our 16S analysis. In high-fat diet-induced obese mice that received CRD-reshaped microbiota via FMT, the CRD-modified microbiota improved metabolic dysbiosis, weakened inflammatory responses and enhanced gut barrier integrity, as well as enriched the abundance of norank_f__Muribaculaceae and Bacteroides . Notably, the short-chain fatty acids were higher, which was associated with the upregulation of UCP2 and subsequent activation of the UCP2-AMPK-ACC1 signal cascade, it potentially promoted the energy homeostasis. Thus, CRD holds a hope to be a candidate of a safe and effective dietary method for the therapy of metabolic diseases via reshaping microbial structure and function.