Cecal Butyrate (Not Propionate) Was Connected with Metabolism-Related Chemicals of Mice, Based on the Different Effects of the Two Inonotus obliquus Extracts on Obesity and Their Mechanisms

[Image: see text] Obesity is a metabolic disease and causes significant changes in host and gut microbial metabolite levels. However, little research has been done on the relationship between host and gut microbial metabolites. Thus, this study investigated the connection of the chemicals, based on the different effects of two Inonotus obliquus extracts on high-fat-diet-induced mice and their mechanisms. In this study, C57BL6/J mice fed with a high-fat diet were given I. obliquus ethanol extract (IOE) and polysaccharide (IOP). (1)H NMR-based metabolomics, 16S rRNA sequencing, and real-time reverse transcription polymerase chain reaction (RT-PCR) were used to detect metabolites, cecal microbes, and expressions of genes in liver. IOE and IOP effectively improved the obesity of mice, including the adjustment of body weight gain, energy intake, energy efficiency, liver glucose metabolism and triglyceride metabolism, tricarboxylic acid (TCA) cycle, and degradation of three major nutrients (carbohydrate, lipid, and protein). IOE significantly increased cecal propionate based on Bacteroides and Akkermansia, thereby inhibiting energy intake and fat accumulation in mice. IOP remarkably improved the level of cecal butyrate by Lactobacillus and the Bacteroidales S24-7 group, resulting in increased energy consumption, and fat degradation by regulating the TCA cycle of the host. Two extracts containing different bioactive substances of I. obliquus improved obesity in mice through different effects on production of cecal microbial metabolites. Moreover, cecal butyrate (not propionate) was connected with chemicals of mice, including four metabolites of the TCA cycle and other metabolism-related chemicals.