Antibiotic-driven dysbiosis in early life disrupts indole-3-propionic acid production and exacerbates allergic airway inflammation in adulthood.
Immunity
; 57(8): 1939-1954.e7, 2024 Aug 13.
Article
em En
| MEDLINE
| ID: mdl-39013465
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.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Asma
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Pyroglyphidae
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Disbiose
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Microbioma Gastrointestinal
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Indóis
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Antibacterianos
Limite:
Animals
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article