Dietary Tryptophan-Mediated Aryl Hydrocarbon Receptor Activation by the Gut Microbiota Alleviates Escherichia coli-Induced Endometritis in Mice
Intestinal microbiota-mediated aryl hydrocarbon receptor (AhR) activation plays an important role in host–microbiota interactions and disease development. However, whether AhR activation mediates infection-induced inflammation in remote organs is not clear. The purpose of this study is to assess the...
Saved in:
Published in | Microbiology spectrum Vol. 10; no. 4; p. e0081122 |
---|---|
Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
1752 N St., N.W., Washington, DC
American Society for Microbiology
31.08.2022
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | Intestinal microbiota-mediated aryl hydrocarbon receptor (AhR) activation plays an important role in host–microbiota interactions and disease development. However, whether AhR activation mediates infection-induced inflammation in remote organs is not clear. The purpose of this study is to assess the effects and underlying mechanism of AhR activation and gut microbiota-mediated dietary tryptophan (Trp) metabolism on infection-induced inflammation using an Escherichia coli (E. coli)-induced endometritis model in mice. We found that AhR activation by 6-formylindolo (3,2-b) carbazole (Ficz), which is an AhR agonist derived from the photooxidation of Trp, alleviated E. coli-induced endometritis by repairing barrier function and inhibiting inflammatory responses, while inhibition of AhR by CH223191, which is a synthetic AhR antagonist, aggravated E. coli-induced endometritis. Gut dysbiosis damaged AhR activation and exacerbated E. coli-induced endometritis in mice, which responded to the reduced abundance of AhR ligand producers, such as Lactobacillus spp. Supplementation with dietary Trp ameliorated E. coli-induced endometritis in a microbiota-dependent manner, which was associated with the production of AhR ligands. Administration of AhR ligands, including indole and indole aldehyde, but not indole-3-propionic acid, rescued the protective effect of Trp on E. coli-induced endometritis in dysbiotic mice. Moreover, consumption of Lactobacillus reuteri (L. reuteri) containing AhR ligand-producing capability also alleviated E. coli-induced endometritis in mice in an AhR-dependent manner. Our results demonstrate that microbiota-mediated AhR activation is a key factor in fighting pathogen-caused inflammation, which leads to a potential strategy to regulate the gut microbiota and metabolism by dietary Trp or probiotics for the intervention of infectious diseases and reproductive health. IMPORTANCE Infection-induced endometritis is a common and frequently occurring disease in humans and animals. Accumulating evidence suggests an important role of the gut microbiota in the development of infection-induced inflammation. Whether and how gut microbiota-mediated AhR activation regulates the pathogenesis of pathogen-induced endometritis remains unknown. The current study found that AhR activation ameliorated E. coli-induced endometritis, and inhibition of AhR produced negative results. Gut dysbiosis reduced the abundance of AhR ligand producers including Lactobacillus spp., damaged AhR activation, and exacerbated E. coli-induced endometritis. Supplementation with dietary Trp, AhR ligands, and L. reuteri containing AhR ligand-producing capability alleviated E. coli-induced endometritis in mice. Our results suggest an important role of microbiota-mediated AhR activation in the pathogenesis of endometritis and provide potential strategies for the intervention of infectious diseases and reproductive health by regulating the gut microbiota and metabolism. |
---|---|
Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 The authors declare no conflict of interest. |
ISSN: | 2165-0497 2165-0497 |
DOI: | 10.1128/spectrum.00811-22 |