Antibiotic-driven dysbiosis in early life disrupts indole-3-propionic acid production and exacerbates allergic airway inflammation in adulthood.
Details
Serval ID
serval:BIB_540ED9A82B4C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Antibiotic-driven dysbiosis in early life disrupts indole-3-propionic acid production and exacerbates allergic airway inflammation in adulthood.
Journal
Immunity
ISSN
1097-4180 (Electronic)
ISSN-L
1074-7613
Publication state
Published
Issued date
13/08/2024
Peer-reviewed
Oui
Volume
57
Number
8
Pages
1939-1954.e7
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Abstract
Antibiotic use in early life disrupts microbial colonization and increases the risk of developing allergies and asthma. We report that mice given antibiotics in early life (EL-Abx), but not in adulthood, were more susceptible to house dust mite (HDM)-induced allergic airway inflammation. This susceptibility was maintained even after normalization of the gut microbiome. EL-Abx decreased systemic levels of indole-3-propionic acid (IPA), which induced long-term changes to cellular stress, metabolism, and mitochondrial respiration in the lung epithelium. IPA reduced mitochondrial respiration and superoxide production and altered chemokine and cytokine production. Consequently, early-life IPA supplementation protected EL-Abx mice against exacerbated HDM-induced allergic airway inflammation in adulthood. These results reveal a mechanism through which EL-Abx can predispose the lung to allergic airway inflammation and highlight a possible preventative approach to mitigate the detrimental consequences of EL-Abx.
Keywords
Animals, Mice, Dysbiosis/immunology, Indoles/pharmacology, Anti-Bacterial Agents/adverse effects, Anti-Bacterial Agents/pharmacology, Gastrointestinal Microbiome/drug effects, Gastrointestinal Microbiome/immunology, Asthma/immunology, Pyroglyphidae/immunology, Lung/immunology, Lung/pathology, Mice, Inbred C57BL, Female, Inflammation/immunology, Disease Models, Animal, Mitochondria/metabolism, Cytokines/metabolism, Hypersensitivity/immunology, Propionates, airway epithelial cells, allergy, antibiotics, early life, gut-lung axis, indole-3-propionic acid, metabolites, microbiota, redox balance, window of opportunity
Pubmed
Web of science
Create date
19/07/2024 10:25
Last modification date
11/09/2024 6:21