Gut-associated microbes of Drosophila melanogaster

Abstract

There is growing interest in using Drosophila melanogaster to elucidate mechanisms that underlie the complex relationships between a host and its microbiota. In addition to the many genetic resources and tools Drosophila provides, its associated microbiota is relatively simple (1-30 taxa), in contrast to the complex diversity associated with vertebrates (> 500 taxa). These attributes highlight the potential of this system to dissect the complex cellular and molecular interactions that occur between a host and its microbiota. In this review, we summarize what is known regarding the composition of gut-associated microbes of Drosophila and their impact on host physiology. We also discuss these interactions in the context of their natural history and ecology and describe some recent insights into mechanisms by which Drosophila and its gut microbiota interact.

Figure 1. The natural and laboratory ecosystem of Drosophila. Drosophila melanogaster lives where it eats both in the wild (A, a fermenting kiwi fruit) and the lab (B, fly vial containing a cooked medium composed of dead yeast, cornmeal, sugar, and agar). Courting of adult female by males, fertilization of eggs, and oviposition all take place on the food source. The embryos hatch and larvae move and feed within their food source. At late stages larvae crawl out of the fruit/medium to pupate and after emerging as adults, begin the cycle anew.

Figure 2. Comparison of the digestive tracts and intestinal epithelial-cell barriers of humans and Drosophila. (A) Diagrammatic representation of the human and adult Drosophila digestive tracts. The digestive tracts of mammals and Drosophila are similar in physiology and function. Both are divided into foregut, midgut, and hindgut segments, based on their embryonic origin, which give rise to specific gut structures and compartmentalized functions. (B) Mammals and Drosophila rely on several mechanisms to limit the contact between microbes in the lumen and intestinal epithelial cells. Mechanisms in common include an acidic zone (the stomach and copper cell region in mammals and Drosophila, respectively (A)), the secretion of mucins to form a protective mucus layer, and the secretion of antimicrobial peptides. In Drosophila, the peritrophic matrix, a layer of chitin and glycoproteins that lines the midgut epithelium, provides a physical barrier against ingested material, such as food particles, microbes, and pore-forming toxins. Reactive oxygen species (ROS) are also an important component of the Drosophila response to microbes, in controlling both levels of dietary microbes and pathogens. In mammals, specialized M cells overlie Peyer’s patches and lymphoid follicles (gut associated lymphoid tissue (GALT)) to facilitate the sampling of the lumen. IgA, produced by plasma cells and transcytosed across epithelial cells, is secreted into the lumen to limit microbes in the mucosa.

Figure 3. The fly-substratum niche and the impacts of gut associated microbes on Drosophila. Drosophila larvae and adults are saprophytic, feeding on microbes growing on decaying fruit (A) These microbes, or others acquired from the environment soon after birth, can also persist in the gut and form stable associations along the life cycle. These microbes have important impacts on host physiology, such as increasing larval growth rate by optimizing host metabolism and inducing the basal epithelial immune response. (B) Yeasts are essential to Drosophila development and nutrition by providing sterols, B vitamins, and RNA. Gut-associated bacteria increase larval growth. In nutrient-limited conditions this has been shown to be due to their impact on TOR-insulin signaling, either by production of acetic acid (Acetobacter pomorum) or increased amino acid metabolism (Lactobacillus plantarum). (C) The Imd pathway is activated upon the recognition of DAP-type peptidoglycan by PGRP-LC. The downstream nuclear translocation of the NF-κB factor Relish activates the transcription of genes encoding antibacterial peptides and negative regulators of the pathway, such as amidase PGRPs and Pirk. Amidase PGPRs reduce the immune response to microbiota by degrading peptidoglycan, while Pirk acts at the level of Imd pathway signaling. The transcription factor Caudal reduces antimicrobial peptide expression in the posterior midgut. This permits persistence of a beneficial microbiota in this segment. Dietary microbes induce the production of ROS by the NAPDH-oxidase Duox, which controls their density in the gut.