Recognition of commensal bacterial peptidoglycans defines Drosophila gut homeostasis and lifespan

Abstract

Commensal microbes in animals have a profound impact on tissue homeostasis, stress resistance, and ageing. We previously showed in Drosophila melanogaster that Acetobacter persici is a member of the gut microbiota that promotes ageing and shortens fly lifespan. However, the molecular mechanism by which this specific bacterial species changes lifespan and physiology remains unclear. The difficulty in studying longevity using gnotobiotic flies is the high risk of contamination during ageing. To overcome this technical challenge, we used a bacteria-conditioned diet enriched with bacterial products and cell wall components. Here, we demonstrate that an A. persici-conditioned diet shortens lifespan and increases intestinal stem cell (ISC) proliferation. Feeding adult flies a diet conditioned with A. persici, but not with Lactiplantibacillus plantarum, can decrease lifespan but increase resistance to paraquat or oral infection of Pseudomonas entomophila, indicating that the bacterium alters the trade-off between lifespan and host defence. A transcriptomic analysis using fly intestine revealed that A. persici preferably induces antimicrobial peptides (AMPs), while L. plantarum upregulates amidase peptidoglycan recognition proteins (PGRPs). The specific induction of these Imd target genes by peptidoglycans from two bacterial species is due to the stimulation of the receptor PGRP-LC in the anterior midgut for AMPs or PGRP-LE from the posterior midgut for amidase PGRPs. Heat-killed A. persici also shortens lifespan and increases ISC proliferation via PGRP-LC, but it is not sufficient to alter the stress resistance. Our study emphasizes the significance of peptidoglycan specificity in determining the gut bacterial impact on healthspan. It also unveils the postbiotic effect of specific gut bacterial species, which turns flies into a "live fast, die young" lifestyle.

High-fat diets induce inflammatory IMD/NFκB signaling via gut microbiota remodeling in Drosophila

“…Lactic and acetic acid bacteria are key gut microbiome members in flies ( Broderick, 2016 ). Acetobacter commensals significantly impact Drosophila development ( Shin et al., 2011 ; Consuegra et al., 2020a , b ), food choice and reproduction ( Elgart et al., 2016 ; Leitao-Goncalves et al., 2017 ), metabolism and behaviors ( Newell and Douglas, 2014 ; Fischer et al., 2017 ), and lifespan ( Obata et al., 2018 ; Onuma et al., 2023 ). Of note, a recent work interestingly uncovered the significance of commensal bacterial PGN specificity in determining the gut bacterial impact on the immune activation ( Onuma et al., 2023 ).…”

Microbiota-derived acetylcholine can promote gut motility in Drosophila melanogaster

“…We tested three isolated strains, Acetobacter persici Ai (A.p) [18], Lactiplantibacillus plantarum Lsi (L.p) [18] and Leuconostoc sp. Leui (Leu) that has 99% identity with L. mesenteroides/pseudomesenteroides [19]. This bacterium is identified specifically in our lab.…”

“…Acetobacter persici Ai (A.p), L. plantarum Lsi (L.p) [18] and Leuconostoc sp. Leui (Leu) [19] were isolated previously from flies maintained in our laboratory. 16S rRNA sequence of Leu has 99% identity with L. mesenteroides or L. pseudomesenteroides.…”

MprF-mediated immune evasion is necessary forLactiplantibacillus plantarumresilience inDrosophilagut during inflammation

“…Flies lacking major AMP classes were recently generated and proved to be instrumental in demonstrating an essential role of AMPs in vivo in the defence against Gram-negative pathogens and in the control of gut microbiota [32–34]. Given that the majority of the Drosophila microbiota members produce DAP-type PGN, they elicit Imd pathway activation in the gut [35–38]. However, in contrast to pathogens, commensals induce a mild AMP response due to the tolerance mechanisms deployed by the host [39].…”