Impact of different hypercaloric diets on obesity features in rats: a metagenomics and metabolomics integrative approach.

ABSTRACT

Diet is considered a key influencing agent affecting the gut microbiome. Dysbiosis of microbial communities contributes to the development of metabolic diseases such as obesity. We aimed to characterize the physiological, microbial and metabolic changes induced by different obesogenic diets to understand the diet-specific modulation of the host-microbiota co-metabolism in rodents. For this purpose, Wistar rats were fed standard, cafeteria (CAF), low-fat (LF), high-fat (HF) and high-fat high-sucrose (HFS) diets for 10 weeks. The CAF diet strongly induced an obese phenotype accompanied by dyslipidemia, hyperleptinemia, insulin resistance and hepatic steatosis, whereas both HF and HFS diets promoted overweight. Concerning the microbiome, CAF feeding induced a rise of the Bacteroidetes-to-Firmicutes ratio, while few microbial genera were altered in the HF or HFS group. Changes in microbial activity according to dietary treatment were also reflected in the disruption of short-chain fatty acid production and bile acid metabolism, which were mainly associated with fiber intake. Urinary metabolomics revealed a significant increase in metabolites related to oxidative stress and metabolic inflammation together with an altered excretion of host-microbiota co-metabolites only in the CAF group. Moreover, several associations between metabolic patterns, physiological status and specific microbial communities were described, helping to elucidate the crucial role of the microbiota in host homeostasis. Overall, our study suggests that different hypercaloric dietary models distinctively influence gut microbiota composition and reveals robust and similar clustering patterns concerning both cecal microbiome and urinary metabolome profiles.