Recovery of the Gut Microbiota after Antibiotics Depends on Host Diet and Environmental Reservoirs

Abstract

That antibiotics alter microbiota composition and increase infection susceptibility is well known, but their generalizable effects on the gut commensal community and dependence on environmental variables remain open questions. Here, we systematically compared antibiotic responses in gnotobiotic and conventional mice across antibiotics, microbiotas, diets, and housing status. We identify remarkable resilience, whereby a humanized microbiota recovers before drug administration ends, with transient oligodominance and taxa-asymmetric reduction in diversity. In general, in vitro sensitivities were not predictive of in vivo responses, underscoring the significance of community context. A fiber-deficient diet exacerbated collapse of the microbiota. We also observed response reprogramming, in which species replacement after ciprofloxacin treatment established resilience to a second treatment, as did transmission through cross-housing. Single-housing drastically disrupted recovery, highlighting the importance of sanitation and environmental reservoirs. Our findings highlight the ability of the commensal microbiota to deterministically adapt to large perturbations, and the translational potential for modulating diet, sanitation, and microbiota composition during antibiotics.