(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.

Humans choose which foods they will eat from multiple options. The use of cafeteria-style diets with rodent models has increased our understanding of how a multichoice food environment affects eating and health. However, the wide variances in energy density, texture, and the content of micronutrients, fiber, and protein can be interpretatively problematic when human foodstuffs are used to create rodent cafeteria diets. We minimized these differences with a custom rodent cafeteria diet (ROD) that varied similarly to a previously used human-foods cafeteria diet (HUM) in fat and sugar content. Here, we used our custom Five-Item Food Choice Monitor to compare the intake and meal patterns of rats offered ROD and HUM in a crossover design. Compared with chow, rats consumed more calories, sugar, and fat and less protein and carbohydrate while on either of the choice diets (p < 0.05). While energy intake was similar between HUM and ROD, there were differences in the responses. Rats consumed more of the low-fat, low-sugar choice on the ROD compared with the nutritionally similar choice on the HUM leading to differences in fat and carbohydrate intake between the diets (p < 0.05). The stability of macronutrient intake while on either choice diet suggests macronutrient intake is determined by the available foods and is strongly regulated. Therefore, interpretative consideration must be given to the nature of food choices in the context of available options when interpreting cafeteria-diet intake.