Sublethal antibiotics collapse gut bacterial populations by enhancing aggregation and expulsion

Abstract

Significance The vast numbers of microbes that reside in the intestines of humans and other animals influence normal physiological functions and, when perturbed, can contribute to many disorders. Antibiotics can dramatically alter gut communities, even at concentrations far below lethal doses, for reasons that remain unclear. We directly imaged native bacterial species inside living larval zebrafish as they reacted to low concentrations of the common antibiotic ciprofloxacin. We found that antibiotics enhanced aggregation of live bacterial cells, resulting in their increased expulsion from the gut by the intestine’s mechanical contractions. Our observations and biophysical model suggest that gut bacterial populations may be especially sensitive to environmental antibiotic contamination, as cell-scale responses are amplified by the material transport characteristic of gastrointestinal systems. Antibiotics induce large and highly variable changes in the intestinal microbiome even at sublethal concentrations, through mechanisms that remain elusive. Using gnotobiotic zebrafish, which allow high-resolution examination of microbial dynamics, we found that sublethal doses of the common antibiotic ciprofloxacin cause severe drops in bacterial abundance. Contrary to conventional views of antimicrobial tolerance, disruption was more pronounced for slow-growing, aggregated bacteria than for fast-growing, planktonic species. Live imaging revealed that antibiotic treatment promoted bacterial aggregation and increased susceptibility to intestinal expulsion. Intestinal mechanics therefore amplify the effects of antibiotics on resident bacteria. Microbial dynamics are captured by a biophysical model that connects antibiotic-induced collapses to gelation phase transitions in soft materials, providing a framework for predicting the impact of antibiotics on the intestinal microbiome.