(P31-057-23) Prebiotic Fibers Engage a Microbiota-Endocrine-Neural Axis To Treat Obesity

Objectives: Obesity is a serious and growing health problem that affects almost half of the US population. One overlooked dietary factor in obesogenic diets is the lack of fibers. Eating dietary fiber-rich foods causes satiation and promotes weight loss. While the underlying mechanisms are unclear, consumption of fibers is correlated with increased satiety hormones and improved gut microbiota profiles in both humans and rodents with obesity. We investigated the causal role of gut hormones and gut microbiota in mediating the satiating effects of dietary fibers (prebiotics).

Methods: We randomized obesity-prone and obesity-resistant male rats to two high-fat diet groups with or without inulin fiber and monitored for changes in energy balance, body composition, gut hormones and microbiome.

Results: Acute and long-term augmentation of dietary inulin in rats decreased calorie intake and reduced adiposity in a dose-dependent manner. These changes correlated with improved gut microbiota profiles and higher plasma peptide YY (PYY) levels. To determine the role of PYY in inulin-induced satiety, we acutely administered PYY receptor (Y2) blocker that attenuated the reduction of caloric intake in inulin-fed animals but had no effect in control rats. To determine whether inulin acts through a vagal sensory pathway to mediate its effects, we used cholecystokinin conjugated with the neurotoxin saporin for gut-selective vagal deafferentation. This approach abolished inulin-induced hypophagia, indicating the necessity of vagal signalling in mediating inulin-induced satiety. Reducing gut microbiota with antibiotics nullified the hypophagic effects of exogenous PYY in obesity-prone rats, highlighting a key role for gut microbiota in PYY-induced satiety. Normalizing gut microbiota with fecal-microbiota transplantation from donor inulin-fed rats to recipient high-fat-fed obese rats increased plasma PYY concentrations and hypophagia.

Conclusions: Together, these data demonstrate that the therapeutic effects of inulin in obesity are mediated by gut microbiota-induced increases in circulating PYY levels that promote hypophagia and adiposity loss via a vagally mediated gut-brain pathway.

Funding Sources: NSERC, Heart & Stroke Foundation of Canada, National Institutes of Health, American Heart Association, and American Neurogastroenterology and Motility Society.