Pathogen Virulence Impedes Mutualist-Mediated Enhancement of Host Juvenile Growth via Inhibition of Protein Digestion.

The microbial environment impacts many aspects of metazoan physiology through largely undefined molecular mechanisms. The commensal strain Lactobacillus plantarum(WJL) (Lp(WJL)) sustains Drosophila hormonal signals that coordinate systemic growth and maturation of the fly. Here we examine the underlying mechanisms driving these processes and show that Lp(WJL) promotes intestinal peptidase expression, leading to increased intestinal proteolytic activity, enhanced dietary protein digestion, and increased host amino acid levels. Lp(WJL)-mediated peptidase upregulation is partly driven by the peptidoglycan recognition and signaling cascade PGRP-LE/Imd/Relish. Additionally, this mutualist-mediated physiological benefit is antagonized upon pathogen infection. Pathogen virulence selectively impedes Lp(WJL)-mediated intestinal peptidase activity enhancement and juvenile growth promotion but does not alter growth of germ-free animals. Our study reveals the adaptability of host physiology to the microbial environment, whereby upon acute infection the host switches to pathogen-mediated host immune defense at the expense of mutualist-mediated growth promotion.

Drosophila microbiota modulates host metabolic gene expression via IMD/NF-κB signaling.

Most metazoans engage in mutualistic interactions with their intestinal microbiota. Despite recent progress the molecular mechanisms through which microbiota exerts its beneficial influences on host physiology are still largely uncharacterized. Here we use axenic Drosophila melanogaster adults associated with a standardized microbiota composed of a defined set of commensal bacterial strains to study the impact of microbiota association on its host transcriptome. Our results demonstrate that Drosophila microbiota has a marked impact on the midgut transcriptome and promotes the expression of genes involved in host digestive functions and primary metabolism. We identify the IMD/Relish signaling pathway as a central regulator of this microbiota-mediated transcriptional response and we reveal a marked transcriptional trade-off between the midgut response to its beneficial microbiota and to bacterial pathogens. Taken together our results indicate that microbiota association potentiates host nutrition and host metabolic state, two key physiological parameters influencing host fitness. Our work paves the way to subsequent mechanistic studies to reveal how these microbiota-dependent transcriptional signatures translate into host physiological benefits.