Gut microbiota dysbiosis in diet-induced obesity. A focus on the influence of genetics, circadian rhythms and potential prebiotics

Identifier:  TDX:3032

Handle: https://hdl.handle.net/20.500.11797/TDX3032

Authors:  Gual Grau, Andreu

Abstract:
The host and its gut microbiota co-live in a mutually beneficial relationship, while the disruption of this equilibrium has been related to pathological states like obesity. Remarkably, gut microbial dysbiosis has a multi-factorial origin beyond the strong impact of diet. In this thesis, we deeply evaluated the influence of genetics, circadian rhythms and potential prebiotics in obesity from a metagenomic perspective. Firstly, we characterized the impact of Westernized and semi-purified diets on gut microbiota and host phenotype in Wistar rats, thus identifying cafeteria diet as the most effective dietary model for inducing severe obesity and gut microbiota dysbiosis. Furthermore, the cafeteria diet caused a strong disruption of bile acid metabolism, SCFA production and urinary metabolome. By contrast, semi-purified diets promoted a modest fat accumulation and minor changes on gut microbiome. Then, the influence of strain and gender upon the microbial responses to cafeteria diet was addressed. Wistar rats were more susceptible to cafeteria diet-induced microbial dysbiosis than F344 animals, which was characterized by an increased Bacteroidetes-to-Firmicutes ratio, whereas obesity development similarly occurred in both strains. In addition, F344 females developed more severe alterations on biometric parameters and gut microbiota than males under a cafeteria feeding. We further evaluated the impact of cafeteria diet and grape seed proanthocyanidins on circadian rhythms of gut microbiota. Whereas the cafeteria diet disturbed the naturally occurring microbial rhythmicity, mainly by altering the cyclical abundance of Lactobacillus, grape seed proanthocyanidins, which can be metabolized by intestinal microbes, restored the microbial signatures of dysbiosis during the active period. Finally, we investigated the prebiotic capacity of several natural ingredients in an in vitro fermentation study with human fecal microbiota. Here, pumpkin skin promoted the largest drop in pH and an inulin-like metabolomic profile in normoweight and obese fecal samples, thus revealing for the first time its prebiotic potential.