Amoxicillin induces gut dysbiosis leading to long term suppression of type-17 immune tone in the lungs
Year: 2026
Type: preprint
Abstract: T-helper (Th)-17 lymphocytes are central mediators of adaptive type 17 immunity. Decreased type-17 signaling increases severity of infections in humans and mice. However, detrimental effects of excessive type 17 responses in autoimmune and other inflammatory diseases highlight a need for type-17 immune calibration to support beneficial host defense requirements. Mechanisms of type 17 calibration are poorly understood. A gut-lung axis has been proposed to coordinate homeostatic protection and acute host defense. Factors that acutely alter the gut microbiome are heterogeneous and include acute intestinal infections, non-infectious colitis, and medical treatments such as antibiotics. How changes in the gut microbiome affect lung immune tone during homeostasis and acute pulmonary infections are also poorly understood. Prior studies have shown that antibiotics reduce expression of IL-17-mediated host defense in the gut. Since gut microbial homeostasis influences Th17 cell numbers in both the intestine and remote tissues, we postulated that antibiotic treatment would result in gut dysbiosis and weakened type-17 host defense in the lungs. We found that amoxicillin induces significant dysbiosis that is long-lasting and that there is a long-term decrease in type-17 tone in the lungs. We also found that in mice lacking the gut mucin, Muc2, Th17 cells increased in the lungs following inflammatory challenge. These findings suggest that antibiotic-induced dysbiosis can decrease lung immune defenses for long periods of time after cessation of antibiotic treatment.
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: G1000448250, Lung Macrophage Programming in Acute Lung Injury, Epithelial A2B-mediated Muc5ac expression protects the intestinal barrier during inflammation., Epithelial Contributions to Lung Immunity, G9000192068, Role of mucin in lung homeostasis and pathophysiology, Function and Regulation of Airway Mucin Glycosylation, Mechanisms of lung macrophage programming by MUC5B during health and disease, Mechanisms Regulating Lung Injury and Early Lung Fibrosis, Multi-Disciplinary Research Training in Respiratory Disease, Center for Mucosal Immunobiology and Rheumatic Disease Pathogenesis, Gut microbiome effects on intestinal barrier function and metabolic syndrome in HIV positive men who have sex with men, G993733062
OpenAlex ID: W7134845249