Gut microbiome profoundly affects many aspects of host physiology and behaviors. Here we report that gut microbiome modulates aggressive behaviors in Drosophila. We found that germ-free males showed substantial decrease in inter-male aggression, which could be rescued by microbial re-colonization. These germ-free males are not as competitive as wild-type males for mating with females, although they displayed regular levels of locomotor and courtship behaviors. We further found that Drosophila microbiome interacted with diet during a critical developmental period for the proper expression of octopamine and manifestation of aggression in adult males. These findings provide insights into how gut microbiome modulates specific host behaviors through interaction with diet during development.

Sucrose, one of the main products of photosynthesis in plants, functions as a universal biomarker for nutritional content and maturity of different fruits across diverse ecological niches. Drosophila melanogaster congregates to lay eggs in rotting fruits, yet the factors that influence these decisions remains uncovered. Here, we report that lactic acid bacteria Enterococci are critical modulators to attract Drosophila to lay eggs on decaying food. Drosophila-associated Enterococci predominantly catabolize sucrose for growing their population in fly food, and thus generate a unique ecological niche with depleted sucrose, but enriched bacteria. Female flies navigate these favorable oviposition sites by probing the sucrose cue with their gustatory sensory neurons. Acquirement of indigenous microbiota facilitated the development and systemic growth of Drosophila, thereby benefiting the survival and fitness of their offspring. Thus, our finding highlights the pivotal roles of commensal bacteria in influencing host behavior, opening the door to a better understanding of the ecological relationships between the microbial and metazoan worlds.

Background: Aberrant aggregation of α-synuclein (α-syn) is a key pathological feature of Parkinson’s disease (PD), but the precise role of intestinal α-syn in the progression of PD is unclear. In a number of genetic Drosophila models of PD, α-syn was frequently ectopically expressed in the neural system to investigate the pathobiology. Method: We investigated the potential role of intestinal α-syn in PD pathogenesis using a Drosophila model. Human α-syn was overexpressed in Drosophila guts, and life span, survival, immunofluorescence and climbing were evaluated. Immunofluorescence, Western blotting and reactive oxygen species (ROS) staining were performed to assess the effects of intestinal α-syn on intestinal dysplasia. High‐throughput RNA and 16S rRNA gene sequencing, quantitative RT‐PCR, immunofluorescence, and ROS staining were performed to determine the underlying molecular mechanism. Results: We found that the intestinal α-syn alone recapitulated many phenotypic and pathological features of PD, including impaired life span, loss of dopaminergic neurons, and progressive motor defects. The intestine-derived α-syn disrupted intestinal homeostasis and accelerated the onset of intestinal ageing. Moreover, intestinal expression of α-syn induced dysbiosis, while microbiome depletion was efficient to restore intestinal homeostasis and ameliorate the progression of PD. Intestinal α-syn triggered ROS, and eventually led to the activation of the dual oxidase (DUOX)–ROS–Jun N-terminal Kinase (JNK) pathway. In addition, α-syn from both the gut and the brain synergized to accelerate the progression of PD. Conclusions: The intestinal expression of α-syn recapitulates many phenotypic and pathologic features of PD, and induces dysbiosis that aggravates the pathology through the DUOX–ROS–JNK pathway in Drosophila. Our findings provide new insights into the role of intestinal α-syn in PD pathophysiology.

Plants generate a plethora of secondary compounds (toxins) that potently influence the breadth of the breeding niches of animals, including Drosophila. Capsaicin is an alkaloid irritant from hot chili peppers, and can act as a deterrent to affect animal behaviors, such as egg laying choice. However, the mechanism underlying this ovipositional avoidance remains unknown. Here, we report that Drosophila females exhibit a robust ovipositional aversion to capsaicin. First, we found that females were robustly repelled from laying eggs on capsaicin-containing sites. Second, genetic manipulations show that the ovipositional aversion to capsaicin is mediated by activation of nociceptive neurons expressing the painless gene. Finally, we found that capsaicin compromised the health and lifespan of flies through intestinal dysplasia and oxidative innate immunity. Overall, our study suggests that egg-laying sensation converts capsaicin into an aversive behavior for female Drosophila, mirroring an adaptation to facilitate the survival and fitness of both parents and offspring.

Background: Since animals frequently encounter a variety of harmful fungi in nature, their ability to develop sophisticated anti-fungal strategies allows them to flourish across the globe. Extensive studies have highlighted the significant involvement of indigenous microbial communities in human health. However, the daunting diversity of mammalian microbiota and host genetic complexity are major obstacles to our understanding of these intricate links between microbiota components, host immune genotype, and disease phenotype. In this study, we sought to develop a bacterium-fungus-Drosophila model to systematically evaluate the anti-fungal effects of commensal bacteria. Results: We isolated the pathogenic fungal strain, Diaporthe FY, which was detrimental to the survival and development of Drosophila upon infection. Using Drosophila as a model system, Drosophila-associated Lactobacillus plantarum functioned as a probiotic, and protected the flies from mortality induced by Diaporthe FY. Our results show that L. plantarum hindered the growth of Diaporthe FY in vitro, and decreased the mortality rate of Diaporthe FY-infected flies in vivo, consequently mitigating the toxicity of Diaporthe FY to the hosts. Additionally, the presence of L. plantarum overrode the avoidance of oviposition on Diaporthe FY-associated substrates. Conclusions: Diaporthe FY was identified as a potential Drosophila pathogen. Commensal L. plantarum mitigated the susceptibility of Drosophila to pathogenic fungi, providing insight into the natural interplay between commensal and pathogenic microbial communities that contribute to animal health and pathogenesis.