Comparative profiling of gut microbiota and metabolome in diet-induced obese and insulin-resistant C57BL/6J mice

Diet-based models are commonly used to investigate obesity and related disorders. We conducted a comparative profiling of three obesogenic diets HFD, high fat diet; HFHF, high fat high fructose diet; and HFCD, high fat choline deficient diet to assess their impact on the gut microbiome and metabolome. After 20 weeks, we analyzed the gut microbiota and metabolomes of liver, plasma, cecal, and fecal samples. Fecal and plasma bile acids (BAs) and fecal short-chain fatty acids (SCFAs) were also examined. Significant changes were observed in fecal and cecal metabolites, with increased Firmicutes and decreased Bacteroidetes in the HFD, HFHF, and HFCD-fed mice compared to chow and LFD (low fat diet)-fed mice. Most BAs were reduced in plasma and fecal samples of obese groups, except taurocholic acid, which increased in HFCD mice's plasma. SCFAs like acetate and butyrate significantly decreased in obesogenic diet groups, while propionic acid specifically decreased in the HFCD group. Pathway analysis revealed significant alterations in amino acid, carbohydrate metabolism, and nucleic acid biosynthesis pathways in obese mice. Surprisingly, even LFD-fed mice showed distinct changes in microbiome and metabolite profiles compared to the chow group. This study provides insights into gut microbiome dysbiosis and metabolite alterations induced by obesogenic and LFD diets in various tissues. These findings aid in selecting suitable diet models to study the role of the gut microbiome and metabolites in obesity and associated disorders, with potential implications for understanding similar pathologies in humans.