The metazoan gut microbiota comprises a rich and diverse community of commensal bacteria species. It plays a vital role to maintain systemic homeostasis in multiple host organs and thus sustains optimal host health. Consequently, various aspects of host development and physiology, ranging from juvenile growth to adult lifespan, are altered in germ-free (GF) animals. We have previous shown that on a low yeast diet, GF Drosophila experience retarded larval growth and delay in development. Interestingly, mono-associating axenic fly embryos with a single strain of the gut commensal species, Lactobacillus plantarum (LpWJL), can re-accelerate growth and partially restore developmental timing, and this growth-promotion effect is mediated through the host ToR signaling pathway.
To identify additional host genetic variants and networks that respond to the growth promotion effect via LpWJL, we conducted a genome-wide association study (GWAS) on the Drosophila Genetic Reference Panel (DGRP) based on the variation in larval growth difference between the GF and their LpWJL –monoxenic siblings among the strains. We obtained a set of polymorphisms associated to genes with novel and unknown functions, as well as genes involved in host metabolism, hormonal signaling and immune response. Here we present the validation of selected candidates implicated in host response to LpWJL –mediated juvenile growth. Specifically, we focus on the role of Dawdle, the activin-like TGF-β ligand that has been shown to regulate host metabolic adaptation to the nutritional environment. In summary, our finding suggests that the genetic basis of the juvenile host response to the presence of the intestinal microbiota is complex and poly-genic.