Genetic Influences of the Microbiota on the Life Span of Drosophila melanogaster

• Published in: Applied and environmental microbiology Vol. 86; no. 10
• Main Authors: Matthews, Melinda K, Wilcox, Hailey, Hughes, Rachel, Veloz, Madeline, Hammer, Austin, Banks, Bethany, Walters, Amber, Schneider, Kyle J, Sexton, Corinne E, Chaston, John M
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 05.05.2020
• Subjects: Aging; Animal behavior; Bacteria; Drosophila melanogaster; E coli; Fruit flies; Fruits; Gene expression; Gene sequencing; Genes; Glucose; Glucose metabolism; Influence; Insects; Invertebrate Microbiology; Life span; Longevity; Metabolism; Metabolites; Metabolomics; Methionine; Microbiota; Microorganisms; Mimicry; Mutants; Mutation; Pyridoxine; Ribonucleic acid; RNA; Spotlight; Strains (organisms); Vitamin B6; MGWA; microbiota; glucose; life span; methionine restriction; metagenome-wide association; vitamin B6; Drosophila melanogaster; Acetobacter; Lactobacillus
• ISSN: 0099-2240; 1098-5336
• DOI: 10.1128/AEM.00305-20

To better understand how associated microorganisms ("microbiota") influence organismal aging, we focused on the model organism We conducted a metagenome-wide association (MGWA) as a screen to identify bacterial genes associated with variation in the life span. The results of the MGWA predicted that bacterial cysteine and methionine metabolism genes influence fruit fly longevity. A mutant analysis, in which flies were inoculated with strains bearing mutations in various methionine cycle genes, confirmed a role for some methionine cycle genes in extending or shortening fruit fly life span. Initially, we predicted these genes might influence longevity by mimicking or opposing methionine restriction, an established mechanism for life span extension in fruit flies. However, follow-up transcriptome sequencing (RNA-seq) and metabolomic experiments were generally inconsistent with this conclusion and instead implicated glucose and vitamin B metabolism in these influences. We then tested if bacteria could influence life span through methionine restriction using a different set of bacterial strains. Flies reared with a bacterial strain that ectopically expressed bacterial transsulfuration genes and lowered the methionine content of the fly diet also extended female life span. Taken together, the microbial influences shown here overlap with established host genetic mechanisms for aging and therefore suggest overlapping roles for host and microbial metabolism genes in organismal aging. Associated microorganisms ("microbiota") are intimately connected to the behavior and physiology of their animal hosts, and defining the mechanisms of these interactions is an urgent imperative. This study focuses on how microorganisms influence the life span of a model host, the fruit fly First, we performed a screen that suggested a strong influence of bacterial methionine metabolism on host life span. Follow-up analyses of gene expression and metabolite abundance identified stronger roles for vitamin B and glucose than methionine metabolism among the tested mutants, possibly suggesting a more limited role for bacterial methionine metabolism genes in host life span effects. In a parallel set of experiments, we created a distinct bacterial strain that expressed life span-extending methionine metabolism genes and showed that this strain can extend fly life span. Therefore, this work identifies specific bacterial genes that influence host life span, including in ways that are consistent with the expectations of methionine restriction.