Microbial mediation of lipid absorption in Drosophila

Johns Hopkins University, Baltimore MD

Investigators

Abstract

PROJECT SUMMARY Since the industrial revolution, western diets have undergone significant transformation. These changes have been associated with increased rates of metabolic disease. Changes in gut microbiota have been linked to increased rates of these diseases, both in humans and mammalian models. However, the mechanism that links the composition of the microbiome to onset of these metabolic diseases is unclear. One proposed mechanism is the increase in lipid absorption observed both in fish and mammalian models, which has been linked to the presence of specific bacterial species. However, a mechanism remains elusive. This proposal aims to study the question of how the microbiome influences lipid absorption in the fruit fly Drosophila melanogaster. Drosophila was selected for this project because of its small, tractable microbiome, relevance to human gut biology, and the existence of a powerful library of existing genetic tools, such as RNAi, overexpression and fluorescent protein lines. Using a combination of high-pressure liquid chromatography, and fluorescent microscopy, I have preliminarily shown that the microbiome of Drosophila melanogaster increases lipid absorption of the fluorescent fatty acid analog BODIPY-C12. In this proposal, I plan to verify this phenotype and establish causative microbes and timing of lipid absorption (Aim 1),and investigate the mechanism of this increase in lipid absorption by conducting a small RNAi screen on host genes thought to be involved in lipid absorption, specifically focusing on the hypothesis that microbial-mediated pH drives changes in the activity of these genes (Aim 2). Successful completion of the proposed aims will strengthen the link between microbial colonization and increased lipid absorption observed previously in vertebrates (I), discover genes important for lipid absorption in Drosophila (II), and establish Drosophila as tractable model for understanding lipid absorption (III).