The gut microbiota drives the impact of bile acids and fat source in diet on mouse metabolism

TLDR

The gut microbiota influences metabolic health, yet how bile acids and dietary fat source interact with intestinal microorganisms to affect host metabolism remains unclear and requires careful interpretation in diet‑induced obesity models. The study aimed to determine how diets enriched in primary bile acids combined with different fat sources affect mouse metabolism. The authors examined gut microbiota composition and function in mice fed these diets, comparing colonized and germ‑free animals over 8 weeks. In colonized male C57BL/6N mice, bile‑acid‑enriched lard diets increased fat mass, impaired glucose tolerance, reduced insulin and enteroendocrine cells, induced fatty liver with elevated hepatic triglycerides and cholesterol esters, and altered gut bacterial communities and metabolic pathways, whereas germ‑free mice were protected.

Abstract

As the gut microbiota contributes to metabolic health, it is important to determine specific diet-microbiota interactions that influence host metabolism. Bile acids and dietary fat source can alter phenotypes of diet-induced obesity, but the interplay with intestinal microorganisms is unclear. Here, we investigated metabolic consequences of diets enriched in primary bile acids with or without addition of lard or palm oil, and studied gut microbiota structure and functions in mice. In combination with bile acids, dietary lard fed to male C57BL/6N mice for a period of 8 weeks enhanced fat mass accumulation in colonized, but not in germ-free mice when compared to palm oil. This was associated with impaired glucose tolerance, lower fasting insulin levels, lower counts of enteroendocrine cells, fatty liver, and elevated amounts of hepatic triglycerides, cholesteryl esters, and monounsaturated fatty acids. Lard- and bile acid-fed mice were characterized by shifts in dominant gut bacterial communities, including decreased relative abundances of Lachnospiraceae and increased occurrence of Desulfovibrionaceae and the species Clostridium lactatifermentans and Flintibacter butyricus. Metatranscriptomic analysis revealed shifts in microbial functions, including lipid and amino acid metabolism. Caution is required when interpreting data from diet-induced obesity models due to varying effects of dietary fat source. Detrimental metabolic consequences of a diet enriched with lard and primary bile acids were dependent on microbial colonization of the host and were linked to hepatic lipid rearrangements and to alterations of dominant bacterial communities in the cecum.