Adult Drosophila melanogaster raised in the absence of symbiotic bacteria have fewer intestinal stem cell divisions and a longer life span than their conventionally reared counterparts. However, we do not know if increased stem cell divisions are essential for symbiont-dependent regulation of longevity. To determine if individual symbionts cause aging-dependent death in Drosophila, we examined the impacts of common symbionts on host longevity. We found that monoassociation of adult Drosophila with Lactobacillus plantarum, a widely reported fly symbiont and member of the probiotic Lactobacillus genus, curtails adult longevity relative to germfree counterparts. The effects of Lactobacillus plantarum on life span were independent of intestinal aging. Instead, we found that association with Lactobacillus plantarum causes an extensive intestinal pathology within the host, characterized by loss of stem cells, impaired epithelial renewal, and a gradual erosion of epithelial ultrastructure. Our study uncovers an unknown aspect of Lactobacillus plantarum-Drosophila interactions and establishes a simple model to characterize symbiont-dependent disruption of intestinal homeostasis.

Background:We know comparatively little about the impact of deregulated intestinal proliferation on an otherwise normal animal. Results: Modified progression through the cell cycle disrupted homeostasis without affecting longevity. Conclusion: Disrupted intestinal homeostasis alone does not shorten the life span of an adult fly. Significance: These questions are of considerable importance, given the relationship between proliferation, dysplasia, aging, and death.

Drosophila melanogaster is an excellent model to explore the molecular exchanges that occur between an animal intestine and associated microbes. Previous studies in Drosophila uncovered a sophisticated web of host responses to intestinal bacteria. The outcomes of these responses define critical events in the host, such as the establishment of immune responses, access to nutrients, and the rate of larval development. Despite our steady march towards illuminating the host machinery that responds to bacterial presence in the gut, there are significant gaps in our understanding of the microbial products that influence bacterial association with a fly host. We sequenced and characterized the genomes of three common Drosophila-associated microbes: Lactobacillus plantarum, Lactobacillus brevis and Acetobacter pasteurianus. For each species, we compared the genomes of Drosophila-associated strains to the genomes of strains isolated from alternative sources. We found that environmental Lactobacillus strains readily associated with adult Drosophila and were similar to fly isolates in terms of genome organization. In contrast, we identified a strain of A. pasteurianus that apparently fails to associate with adult Drosophila due to an inability to grow on fly nutrient food. Comparisons between association competent and incompetent A. pasteurianus strains identified a short list of candidate genes that may contribute to survival on fly medium. Many of the gene products unique to fly-associated strains have established roles in the stabilization of host-microbe interactions. These data add to a growing body of literature that examines the microbial perspective of host-microbe relationships.

The microbiome of Drosophila promotes intestinal stem cell division through evolutionarily conserved biochemical pathways. As such, axenic flies have lower rates of gut stem cell division than age-matched wild type counterparts. Additionally, flies with a full consortium of symbiotic bacteria are shorter lived than those maintained in the absence of a microbiome. However, we do not know if stem cell division is essential for symbiontdependent regulation of adult fly lifespan. To determine if individual symbionts cause aging-dependent death in Drosophila, we examined the impacts of common symbionts on host longevity. In this study, we found that mono-association of adult Drosophila with Lactobacillus plantarum, a widely reported fly symbiont, and member of the probiotic Lactobacillus genus, curtails adult longevity relative to germ-free counterparts. However, the effects of plantarum on lifespan were independent of intestinal aging. Instead, we found that association with plantarum causes an extensive intestinal pathology within the host, characterized by loss of intestinal stem cells, impaired epithelial renewal, and a gradual erosion of epithelial integrity. Our study uncovers an unknown aspect of Lactobacillus plantarum-Drosophila interactions, and establishes a simple model to characterize symbiont-dependent disruption of intestinal homeostasis.