Amoxicillin induces gut dysbiosis leading to long term suppression of type-17 immune tone in the lungs.

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.