(1) High-fat (HF) diet leads to gut microbiota dysbiosis which is associated with systemic inflammation. Bacterial-driven inflammation is sufficient to alter vagally mediated satiety and induce hyperphagia. Promoting bacterial fermentation improves gastrointestinal (GI) epithelial barrier function and reduces inflammation. Resistant starch escape digestion and can be fermented by bacteria in the distal gut. Therefore, we hypothesized that potato RS supplementation in HF-fed rats would lead to compositional changes in microbiota composition associated with improved inflammatory status and vagal signaling. (2) Male Wistar rats (n = 8/group) were fed a low-fat chow (LF, 13% fat), HF (45% fat), or an isocaloric HF supplemented with 12% potato RS (HFRS) diet. (3) The HFRS-fed rats consumed significantly less energy than HF animals throughout the experiment. Systemic inflammation and glucose homeostasis were improved in the HFRS compared to HF rats. Cholecystokinin-induced satiety was abolished in HF-fed rats and restored in HFRS rats. HF feeding led to a significant decrease in positive c fiber staining in the brainstem which was averted by RS supplementation. (4) The RS supplementation prevented dysbiosis and systemic inflammation. Additionally, microbiota manipulation via dietary potato RS prevented HF-diet-induced reorganization of vagal afferent fibers, loss in CCK-induced satiety, and hyperphagia.

There is accumulating evidence that the gut microbiota and its composition dynamics play a crucial role in regulating the host physiological functions and behavior. Diet composition is the primary modulator of bacterial richness and abundance in the gastrointestinal (GI) tract. Macronutrient (fat, sugar and protein) and fiber contents are especially important in determining microbiota composition and its effect on health outcomes and behavior. In addition to food composition, time of intake and eating patterns have recently been shown to significantly affect gut bacterial make up. Diet-driven unfavorable microbiota composition or dysbiosis can lead to an increased production of pro-inflammatory byproducts such as lipopolysaccharide (LPS). Increased inflammatory potential is associated with alteration in gut permeability, resulting in elevated levels of LPS in the bloodstream, or metabolic endotoxemia. We have found that a chronic increase in circulating LPS is sufficient to induce hyperphagia in rodents. Chronic LPS treatment appears to specifically impair the gut-brain axis and vagally-mediated satiety signaling. The vagus nerve relays information on the quantity and quality of nutrients in the GI tract to the nucleus of solitary tract in the brainstem. There is evidence that microbiota dysbiosis is associated with remodeling of the vagal afferent pathway and that normalizing the microbiota composition in high fat diet (HFD) fed rats is sufficient to prevent vagal remodeling. Taken together, these data support a role for the microbiota in regulating gut-brain communication and eating behavior. Bacteria-originating inflammation may play a key role in impairment of diet-driven satiety and the development of hyperphagia.