Toll links metabolism and microbiota in the Drosophila intestine

Peptidoglycan recognition protein SA (PGRP-SA) is an extracellular recognition protein, which interacts with the peptidoglycan of Gram-positive bacteria and activates the Toll signalling pathway. While many studies have described the interaction of PGRP-SA with pathogenic bacteria, studies on its response to commensal bacteria is lacking. Using Drosophila melanogaster as a model organism, we demonstrate the relationship between PGRP-SA with the indigenous gut microbiota, and how the activity of mTOR influences this relationship. Our results reveal that PGRP-SA is essential to maintain microbial load and retain Lactobacillaceae in young flies. Moreover, inhibition of the activity of mTOR restores the microbiota of PGRP-SA mutant seml flies in a density dependent manner. Translational regulation factor, 4E-BP, whose levels are dictated by both Toll and mTOR pathway of the host, mediates this host-microbiome interaction. Our results give an insight into how host factors maintain indigenous microbiota in a healthy gut. This can help us better understand the genetic basis of variation in the composition of gut bacteria, and assist in developing measures to tackle microbiota induced disorders in the future.