The Gut Microbiota of Drosophila melanogaster: A Model for Host–Microbe Interactions in Metabolism, Immunity, Behavior, and Disease

The gut microbiota of Drosophila melanogaster offers a simplified yet powerful system to study conserved mechanisms of host-microbe interactions. Unlike the highly complex mammalian gut microbiota, which includes hundreds of species, the fly gut harbors a small and defined community dominated by Lactobacillus and Acetobacter. Despite its low diversity, this microbiota exerts profound effects on host physiology. Commensal bacteria modulate nutrient acquisition, regulate insulin/TOR signaling, and buffer dietary imbalances to support metabolic homeostasis and growth. They also influence neural and behavioral traits, including feeding preferences, mating, and aggression, through microbial metabolites and interactions with host signaling pathways. At the immune level, microbial molecules such as peptidoglycan, acetate, uracil, and cyclic dinucleotides activate conserved pathways including Imd, Toll, DUOX, and STING, balancing antimicrobial defense with tolerance to commensals. Dysbiosis disrupts this equilibrium, accelerating aging, impairing tissue repair, and contributing to tumorigenesis. Research in Drosophila demonstrates how a low-diversity microbiota can shape systemic host biology, offering mechanistic insights relevant to human health and disease.