Our digestive tract hosts a microbiota made of bacteria, viruses and other non-pathogenic fungi. A permanent dialogue exists between this gut microbiota and the tissues and organs of the host which contributes to the normal development of the digestive tract and of its immune system. Gut associated bacteria also play an endocrine role in producing metabolites that after crossing the intestinal wall can modulate the function of organs located at a distance from the intestine. Therefore, aberrations in the intestinal microbial population, known as dysbiosis, not only cause local pathologies such as inflammatory bowel diseases, but also affect their hosts far more widely, for example by influencing their behavior by acting on the nervous system.

The team of Julien Royet, at the Institute of Developmental Biology of Marseille, studies the molecular dialogues between the microbiota and the host using the Drosophila model system. Initial work by the team has demonstrated that the peptidoglycan produced by intestinal bacteria that activates the intestinal host’s immune system and is also able to diffuse into the body to alter the activity of some neurons in the central nervous system (Kurz et al., 2017). In a new study published in Cell Host and Microbe, the team demonstrates how Drosophila has developed a defense system that uses two versions of the same peptidoglycan digesting enzyme to simultaneously monitor its immunogenicity locally in the gut and prevent its diffusion into the rest of the body. In the absence of this enzyme, adult flies show signs of tissue degeneration related to the invasion of peptidoglycan in the body and have a shorter lifespan (Charroux et al., 2018).

This work performed in Drosophila opens up new perspectives for understanding the endocrine roles of peptidoglycan derived from microbiota also in mammals. Recent results suggest that peptidoglycan could also serve as a circulating metabolite and modulate host physiology and behavior in mice (Arentsen et al, 2017).

Image confocale d’un tube digestif de Drosophila mutante pour le gène PGRP-LB et infectée par la bactérie Erwinia carotorova. L'activation du gène rapporteur NF-κB (en rouge) dans les entérocytes est supprimée dans les cellules surexprimant l'isoforme PGRP-LB intracellulaire PGRP-LBPA :: EGFP (en vert). Les noyaux sont colorés au Dapi (bleu). L'image a été acquise par Bernard Charroux.

Confocal image of an adult Drosophila midgut mutant for the PGRP-LB locus and infected with the bacteria Erwinia carotovora. Activation of the NF-κB reporter gene (Diptericin-Cherry in Red) in enterocytes is cell-autonomously suppressed in clones overexpressing the intracellular PGRP-LB isoform PGRP-LBPA::EGFP (in Green). Nuclei are stained with Dapi (Blue). The image was acquired by Bernard Charroux.

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