Dietary Prebiotic Fiber Improve Energy Balance and Cardiometabolic Health by Modulating the Gut Microbiota

Background: Fermentation of prebiotic fibers selectively alter gut microbiota, generate short-chain fatty acids (SCFA), stimulate gut hormones like peptide YY (PYY) and cholecystokinin (CCK), and promote satiety. However, the neurohormonal mechanisms, the role of gut microbiota in fiber-induced satiety and their effects on stroke prevention remains unclear. Additionally, the mechanisms of glucose homeostasis and the role of gut microbiota in diabetes require further exploration. Objective: I explored 1) the effects of dietary prebiotics and SCFAs on energy balance, gut microbiota composition, cardiovascular health and stroke prevention; 2) whether fiber-induced alteration in gut microbiota mediate gut satiety hormone- PYY and CCK signaling to promote satiety; 3) whether impaired insulin signaling and altered gut microbiota are linked to diabetes in cats. Methods: Male obese and hypertensive stroke-prone rats were fed high-fat diets supplemented with either prebiotic-inulin, pectin, resistant starch type-4 (RS-4) or guar gum and either free-form or microencapsulated SCFAs- acetate and/or propionate and butyrate. Fecal microbiota transplantation (FMT) and gut hormone receptor antagonists (PYY-Y2, CCK-1, serotonin-5-HT3 receptors) were used to explore the roles of microbiota and hormones in fiber-induced satiety. Measurements included food intake, energy expenditure, body weight and composition, gut microbiota composition, cardiovascular health, gut barrier function and stroke risks. Additionally, client owned cats were categorized to either lean, overweight or diabetic. Markers of insulin and incretin signaling were analyzed at mRNA and protein levels and their association with the gut microbiota was assessed. Results: The primary findings from my study objectives were: 1) pectin and RS-4 lowered food intake and body weight partly via engaging PYY-Y2 and CCK-1 receptors, also improving gut microbial diversity and composition; 2) FMT from inulin-fed donors recapitulated satiety in naïve obese recipients, raised plasma PYY and CCK levels and attenuated hypophagic effects of inulin FMT via PYY and CCK signaling; 3) encapsulated propionate and butyrate reduced caloric intake dose-dependently, shifted metabolism to fat oxidation, and selectively enriched beneficial bacterial taxa in the gut; 4) Low-dose inulin and SCFAs reduced hypertension, improved gut barrier function and gut microbiota composition and, protected stroke-prone rats against cardiovascular insults. Notably, inulin induced hypophagia was partly mediated by CCK and 5-HT3 signaling and butyrate was 5-HT3 dependent; 5) in cats, obese and diabetic states involved deficits in insulin synthesis and incretin signaling in the pancreas, and impaired insulin signaling in the muscle and liver, ectopic lipid deposition in the liver and muscle, distinct microbial dysbiosis, and decreased Bacteroidota abundance. Conclusion: Prebiotic fibers and SCFAs improve energy balance, cardiovascular health and, metabolic outcomes by modulating gut microbiota and gut satiety hormone signaling. Notably, disruptions in insulin signaling and gut microbiota in overweight and diabetic cats underscore cross-species strategy to tackle metabolic disorders from a One Health perspective.