New Prebiotics to Ameliorate High-Fat Diet-Induced Obesity and Diabetes via Modulation of Microbiome-Gut-Brain Axis

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Role of gut microbiome in obesity and diabetes became apparent from several independent studies, indicating that gut microbiome modulators like prebiotics may improve microbiome perturbations (dysbiosis) to ameliorate metabolic derangements. We isolated water soluble, non-digestible polysaccharides from 5 foods (acorn, quinoa, sunflower, pumpkin and sago seeds) and assessed their impact on amelioration of high fat diet (HFD)-induced obesity and diabetes in mice and human microbiome using fecal slurry culture model. During isolation, purification, biochemical and digestion resistance characterization, and fermentation pattern by human fecal microbiome, we selected acorn and sago derived prebiotics, on the basis of purity, protein contamination and yield. All prebiotics increased short chain fatty acid (SCFA) production along with enhanced microbial diversity. Feeding of acorn and sago derived prebiotics supplemented HFD (5%) for 8 weeks, significantly reduced diet induced glucose intolerance and insulin resistance, without affecting adiposity. Beneficial effects of acorn and sago derived prebiotics were superior than inulin-feeding. Feeding of both prebiotics and inulin increased diversity of gut microbiome and enhanced SCFA production into the mice gut. Metabolic function was positively correlated with increased food conversion ratio indicating enhanced whole body metabolic rate by prebiotic feeding. Gastrointestinal motility was enhanced without changing food intake, after probiotic intervention. Hypothalamic energy signaling in terms of increased pro-opiomelanocortin and decreased agouti-related peptide and neuropeptide Y expression, was modulated by prebiotics administration. These results indicate that newly isolated prebiotics ameliorate HFD-induced defects of glucose metabolism via modulating microbiome-gut-brain axis, and can be used to prevent/treat diet induced obesity and diabetes. Disclosure S. Ahmadi: None. R.K. Nagpal: None. S. Wang: None. H. Yadav: None.