Antibiotic-driven dysbiosis in early life disrupts indole-3-propionic acid production and exacerbates allergic airway inflammation in adulthood

• DOI: 10.1016/j.immuni.2024.06.010
• Publication Date: 2024-07-15T14:31:52Z
• Authors: Olaf Perdijk; Alana Butler; Matthew Macowan; Roxanne Chatzis; Edyta Bulanda; Rhiannon D. Grant; Nicola L. Harris; Tomasz P. Wypych; Benjamin J. Marsland
• Keywords: Indoles; antibiotics; redox balance; Mice; SDG 3 - Good Health and Well-being; gut-lung axis; window of opportunity; microbiota; Hypersensitivity; early life; Animals; Lung; metabolites; Inflammation; Pyroglyphidae; allergy; Asthma; indole-3-propionic acid; Anti-Bacterial Agents; Gastrointestinal Microbiome; Mitochondria; Mice, Inbred C57BL; Disease Models, Animal; Dysbiosis; Cytokines; Female; airway epithelial cells; Propionates

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.