The Drosophila model for microbiome research

Abstract

The gut microbiome is increasingly recognized to play an important role in shaping the health and fitness of animals, including humans. Drosophila is emerging as a valuable model for microbiome research, combining genetic and genomic resources with simple protocols to manipulate the microbiome, such that microbiologically sterile flies and flies bearing a standardized microbiota can readily be produced in large numbers. Studying Drosophila has the potential to increase our understanding of how the microbiome influences host traits, and allows opportunities for hypothesis testing of microbial impacts on human health. Drosophila is being used to investigate aspects of host-microbe interactions, including the metabolism, the immune system and behavior. Drosophila offers a valuable alternative to rodent and other mammalian models of microbiome research for fundamental discovery of microbiome function, enabling improved research cost effectiveness and benefits for animal welfare.

Fig. 1|. The Drosophila gut microbiome is amenable to manipulation, to generate axenic flies (i.e. microbiologically sterile, often referred to as “germ-free”) and gnotobiotic flies (i.e. with a standardized microbiota).

To produce axenic flies, eggs are rinsed in hypochlorite, which removes all surface microorganisms, and then aseptically transferred to sterile medium, on which the insect develops to adulthood. Microbes of choice can be added to the vials containing axenic insects. Both larvae and adults feed readily on microorganisms, so establishing an association.

Fig. 2|. The organization of the Drosophila gut.

The gut comprises three regions, the foregut, midgut and hindgut, each of which contains morphologically, genetically and functionally distinct regions^,,. The gut epithelium is bounded by a stable chitinous layer in the foregut and hindgut and a dynamic layer, the peritrophic envelope in the midgut; the adult has a single extensible foregut evagination, the crop and the larva has four proximal midgut ceca; and the Malpighian tubules are strictly oriented, with the right pair (dorsal view) extending anteriorly and the left pair extending posteriorly (the tips are commonly attached to the distal end of the hindgut)^,.

Fig. 3|. Contribution of the gut microbiota to Dmsophila nutrition.

The illustrated experimental design comprises axenic Drosophila and Drosophila with two alternative standardized microbiota (an ineffective microbiota in gnotobiotic-1, i.e., which does not promote insect performance and an effective microbiota in gnotobiotic-2, which does promote insect performance), a. The dietary analysis compares the performance that is lifespan, growth rate, fecundity etc on diets containing and lacking the nutrient (X) of interest, b. The metabolic analysis compares the concentration of the nutrient X or related metabolite and its biosynthesis in Drosophila. The values are for illustration, and the magnitude of differences may vary.