Dietary Adaptation of Microbiota in Drosophila Requires NF-κB-Dependent Control of the Translational Regulator 4E-BP

Cell Rep. 2020 Jun 9;31(10):107736. doi: 10.1016/j.celrep.2020.107736.

Abstract

Dietary nutrients shape complex interactions between hosts and their commensal gut bacteria, further 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 associations. Using Drosophila, we show here that nuclear factor κB (NF-κB)/Relish, an innate immune transcription factor emerging as a signaling node linking nutrient-immune-metabolic interactions, is vital to adapt gut microbiota species composition to host diet macronutrient composition. We find 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 diet-dependent transcriptional inducibility of the cap-dependent translation inhibitor 4E-BP/Thor to control microbiota composition. Furthermore, maintaining cap-dependent translation in response to dietary adaptation is critical to amplify host-Lactobacillus associations. These results highlight that NF-κB-dependent host signaling mechanisms, in coordination with host translation control, shape diet-microbiota interactions.

Keywords: 4E-BP; Drosophila; NF-kB; Relish; cap-dependent translation; commensal bacteria; diet; holobiont; immune-metabolic integration; intestine.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Diet
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / metabolism
  • Drosophila melanogaster / microbiology*
  • Female
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Microbiota*
  • NF-kappa B / metabolism*
  • Peptide Initiation Factors / metabolism*
  • Signal Transduction

Substances

  • Drosophila Proteins
  • Intracellular Signaling Peptides and Proteins
  • NF-kappa B
  • Peptide Initiation Factors
  • Thor protein, Drosophila