The role of gut microbiota and diet in lipid metabolism

The large community of microorganisms in the intestine (microbiota) has been identified as an additional metabolic organ in our body. However, the microbial role in dietary lipid absorption in the intestine is unclear. Improved understanding of the trialogue between dietary nutrients, microbiota and host lipid metabolism can help develop strategies for decreased or increased absorptive capacity as respective treatments for obesity or malnutrition. Here, we use in vivo imaging of fluorescent fatty acid analogues to investigate the effect of microbiota and nutrients on dietary fatty acid absorption in a zebrafish host. Our results demonstrate that the microbiota stimulates fatty acid uptake and lipid droplet accumulation in the intestinal epithelium. The microbiota promotes an increase in enterocyte lipid droplet number, but not size in a diet-dependent manner. We show that the presence of microbial community also results in enhanced dietary fatty acid absorption into the liver and non-gastrointestinal tissues. These findings show that the microbiota stimulates intestinal and extra-intestinal fatty acid absorption in a diet-dependent manner. To determine whether diet affects the zebrafish microbial community composition, we performed sequencing of the bacterial 16S ribosomal RNA gene in gut and water samples from colonized zebrafish under different dietary conditions. Our analysis of bacterial community composition is the first one to show that dietary nutrients promote intestinal Firmicutes abundance in the zebrafish host. Even in the absence of bacterial competition, the Firmicutes primary isolate Exiguobacterium sp. can't survive and colonize the intestine under starved conditions. These findings indicate that Firmicutes survival and growth may require a nutrient-rich environment. Finally, we tested whether the diet-induced increase in intestinal Firmicutes abundance could be partially responsible for the observed increase in lipid droplet number in fed zebrafish colonized with the microbiota. Colonization of germ-free zebrafish with single bacterial strains revealed that lipid droplet number is increased by Firmicutes and lipid droplet size is increased by other bacterial types. These results indicate that the microbiota stimulates intestinal and extra-intestinal fatty acid absorption and that different microbial members mediate intestinal fatty acid absorption via distinct mechanisms. This work demonstrates novel interactions between nutrients and microbiota that enhance dietary fat absorption.Doctor of Philosoph