A Role for Host-Signaling in the Adaptation of the Gut Microbiota to Imbalanced Dietary Conditions in Drosophila

Abstract

Dietary nutrients shape complex interactions between hosts and their commensal gut bacteria. The composition of commensal bacterial species can thus shift in response to changes in host dietary nutrient availability, promoting flexibility in host-microbiota associations that can drive nutritional symbiosis. However, it remains less clear if diet-dependent host signaling mechanisms also influence these indispensable diet-microbiota interactions. Using Drosophila, we show here that nuclear factor kB (NF-kB)/Relish, an innate immune transcription factor emerging as a critical signaling node linking nutrient-immune-metabolic interactions, is vital to adapt gut microbiota species composition to host diet macronutrient composition. We found that Relish is required within midgut enterocytes to amplify host-Lactobacillus associations, an important bacterial mediator of nutritional symbiosis, and thus modulate microbiota composition in response to dietary adaptation. Relish limits the diet-dependent transcriptional inducibility of the cap-dependent translation inhibitor 4E-BP/Thor to control both nascent protein synthesis and microbiota composition. Furthermore, maintaining cap-dependent translation in response to dietary adaptation is critical to amplify host-Lactobacillus associations. These results highlight that NF-kB-dependent host signaling mechanisms, in coordination with specific host translation control, shape diet-microbiota interactions.