Abstract
Although microbiome–host interactions are usual at steady state, gut microbiota dysbiosis can unbalance the physiological and behavioral parameters of the host, mostly via yet not understood mechanisms. Using the Drosophila model, we investigated the consequences of a gut chronic dysbiosis on the host physiology. Our results show that adult flies chronically infected with the non-pathogenic Erwinia carotorova caotovora bacteria displayed organ degeneration resembling wasting-like phenotypes reminiscent of Metabolic Syndrome associated pathologies. Genetic manipulations demonstrate that a local reduction of insulin signaling consecutive to a peptidoglycan-dependent NF-κB activation in the excretory system of the flies is responsible for several of the observed phenotypes. This work establishes a functional crosstalk between bacteria-derived peptidoglycan and the immune NF-κB cascade that contributes to the onset of metabolic disorders by reducing insulin signal transduction. Giving the high degree of evolutionary conservation of the mechanisms and pathways involved, this study is likely to provide a helpful model to elucidate the contribution of altered intestinal microbiota in triggering human chronic kidney diseases.
Highlights
To cite this version: Olivier Zugasti, Raphäel Tavignot, Julien Royet
Our results demonstrate that a continuous activation of NF-κB signaling by bacteria-derived PGN induces fluid accumulation as well as fat body and ovary wasting, a systemic phenotype relevant to the wasting syndrome caused by metabolic disorders and reminiscent of Metabolic Syndrome (MetS) in mammals[31,32]
This study establishes a clear crosstalk between bacteria-derived PGN and an immune NF-κB signaling that contributes to the onset of metabolic disorders in Drosophila
Summary
Gut bacteria-derived peptidoglycan induces a metabolic syndrome-like phenotype via NF-κB-dependent insulin/PI3K signaling reduction in Drosophila renal system. HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. OPEN Gut bacteria‐derived peptidoglycan induces a metabolic syndrome‐like phenotype via NF‐κB‐dependent insulin/PI3K signaling reduction in Drosophila renal system. Using the Drosophila model, we investigated the consequences of a gut chronic dysbiosis on the host physiology. Our results show that adult flies chronically infected with the non-pathogenic Erwinia carotorova caotovora bacteria displayed organ degeneration resembling wasting-like phenotypes reminiscent of Metabolic Syndrome associated pathologies. This work establishes a functional crosstalk between bacteria-derived peptidoglycan and the immune NF-κB cascade that contributes to the onset of metabolic disorders by reducing insulin signal transduction. Giving the high degree of evolutionary conservation of the mechanisms and pathways involved, this study is likely to provide a helpful model to elucidate the contribution of altered intestinal microbiota in triggering human chronic kidney diseases
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