Cafeteria diet exposure, and not weight gain propensity, impacts gut microbiota of rats - a within laboratory...

Preclinical studies have implicated the microbiota in body weight control, but its translation to humans remains uncertain, partly owing to methodological variability in assessing the relationship between diet-induced obesity and microbiota composition. We performed an internal meta-analysis to determine whether the propensity for diet-induced obesity, defined by relative weight gain due to a high-fat, high-sugar "cafeteria" diet, is associated with changes in microbiota composition. We collated fecal microbiome data from 12 studies using our validated model of diet-induced obesity (208 male and 74 female Sprague-Dawley rats; 3.5-13 weeks of chow (control) or cafeteria diet) and determined whether the alpha diversity and composition of the gut microbiota differed between obese-prone and obese-resistant rats. We found consistent effects of cafeteria diet exposure on the microbiota, with marked changes in overall composition, and reduced microbial richness and evenness. Furthermore, specific obesity-associated microbial genera, such as Bacteroides and Blautia, were enriched by the cafeteria diet. Critically, alpha diversity measures and the gut microbiota composition did not differ between obese-prone and obese-resistant rats in either diet group. Our findings suggest that while the microbiota is substantially altered by cafeteria diet intake, these changes appear unrelated to individual susceptibility to weight gain, highlighting the role of additional host factors in modulating diet-induced obesity.