Medium-chain inulin alleviates the obesity and improves systemic health in diet-induced obese mice via mediating the gut microbiome and metabolome

Abstract Background Inulin is well known as a natural dietary fiber with multiple beneficial effects on promoting the physiological and intestinal health of hosts. However, it is unclear whether medium-chain inulin can inhibit high-fat diet (HFD)-induced obesity in mice and its mechanism(s) that underlie such effects. In this study, we tested the hypothesis that medium-chain inulin consumption can counteract the obesity in HFD-fed mice by selectively modulating the gut microbiota, metabolome, and metabolic pathways. Results The results shown that the medium-chain inulin is a polymer primarily consisting of fructose linked 2,1 glycosidic bonds with an average degree polymerization of 12. Among them, molecules of different chain lengths form spherical or cross-linked network spatial structures by folding and coiling. Medium-chain inulin supplementation (3% or 5%) reduced lipid deposition in tissues, ameliorated intestinal health, and thus prevented diet-induced obesity in mice. Furthermore, dietary inclusion of inulin shaped a significantly different microbial community by specially increasing the abundances of Bacteroidota , Faecalibaculum , Bifidobacterium , Parasutterella , Lactobacillaceae , Bacteroides , Clostridium_sensu_stricto_1 , and Akkermansia in inulin-supplemented groups compared with the HFD group. Additionally, dietary inulin supplementation enhanced the concentrations of nicotinamide, indole-3-acetate, 5-hydroxytryptophan, maltose, taurocholic acid, aldosterone 5α-dihydrotestosterone, and corticosterone in gut content of HFD-fed mice, and thus modulated certain energy utilization-related metabolic pathways. Especially, those significantly modulated microbes and metabolites by inulin supplementation positively correlated with ameliorated healthy parameters. Therefore, medium-chain inulin inhibits HFD-induced obesity by specifically modulating key gut microbes and metabolites, thereby affecting the inulin-gut microbiota/metabolome-tissue (phenotype) axis. Conclusions Taken together, dietary inulin supplementation improved the gut barrier and physiological health, while alleviated HFD-induced obesity and complications of mice, including fat deposition and metabolic disorders, etc. This beneficial effect was attributed to the fact that feeding medium-chain inulin could specifically promote certain key beneficial gut bacteria and metabolites, and thus arouse energy utilization-related metabolic pathways alteration. Thus, medium-chain inulin can be employed as a potential functional food or therapeutic agent to prevent or treat diet-induced obesity in the host.