Host Genetic Control of the Microbiota Mediates the Drosophila Nutritional Phenotype

Abstract

A wealth of studies has demonstrated that resident microorganisms (microbiota) influence the pattern of nutrient allocation to animal protein and energy stores, but it is unclear how the effects of the microbiota interact with other determinants of animal nutrition, including animal genetic factors and diet. Here, we demonstrate that members of the gut microbiota in Drosophila melanogaster mediate the effect of certain animal genetic determinants on an important nutritional trait, triglyceride (lipid) content. Parallel analysis of the taxonomic composition of the associated bacterial community and host nutritional indices (glucose, glycogen, triglyceride, and protein contents) in multiple Drosophila genotypes revealed significant associations between the abundance of certain microbial taxa, especially Acetobacteraceae and Xanthamonadaceae, and host nutritional phenotype. By a genome-wide association study of Drosophila lines colonized with a defined microbiota, multiple host genes were statistically associated with the abundance of one bacterium, Acetobacter tropicalis. Experiments using mutant Drosophila validated the genetic association evidence and reveal that host genetic control of microbiota abundance affects the nutritional status of the flies. These data indicate that the abundance of the resident microbiota is influenced by host genotype, with consequent effects on nutrient allocation patterns, demonstrating that host genetic control of the microbiome contributes to the genotype-phenotype relationship of the animal host.

FIG 1

Bacterial communities and phenotypic traits of 79 Drosophila lines from DGRP. (A) Microbiota composition was assessed by pyrosequencing with OTUs called at 97% sequence identity (see also Data Set S1 in the supplemental material). (B to E) Nutritional indices (in micrograms per milligram [dry weight]), with data represented as means ± standard errors of the means (SEMs) (error bars). In each panel, Drosophila lines are ordered by the sum of Acetobacter and Lactobacillus species (A) or by mean nutritional index value (B to E).

FIG 2

Host genetic control of the microbiota. (A) CFU counts per fly of A. tropicalis in five-species gnotobiotic DGRP lines (colonized with Acetobacter pomorum DmCS_004, A. tropicalis DmCS_006, Lactobacillus brevis DmCS_003, L. fructivorans DmCS_002, and L. plantarum DmCS_001), ranked by CFU abundance, and expressed as log₁₀(number of CFUs +1). The contribution of genotype to the total variance (77.8%) was calculated as the square of the standard deviation when DGRP genotype was included as a random effect in the linear mixed model (LMM). (B) Validation of A. tropicalis abundance GWA. Differences between mutant and control lines each raised with the defined five-species microbiota were identified using a linear mixed model. Data are represented as means ± SEMs. (C) Mutants with altered microbiota composition have altered nutritional status. TAG content was measured in five-species gnotobiotic fly lines with mutations in genes that exert genetic control over the microbiota (CG42575, dnc) relative to background controls (bg). (D) Host genetic control of the microbiota mediates fly leanness. TAG content was measured in three-species (Lactobacillus brevis, L. fructivorans, and L. plantarum) gnotobiotic mutant fly lines (omission of Acetobacter species relieves host genetic control of Acetobacter-mediated TAG effects). In panels C and D, each symbol represents the value for an individual fly, and the horizontal bar shows the mean for the group. The data were evaluated by LMM and analysis of variance (ANOVA), with all statistical results shown in Table S1 in the supplemental material. Values that are significantly different are indicated by asterisks as follows: *, P < 0.05, ** P ≤ 0.01, *** P ≤ 0.001. bg, background.