Biophysical consequences of sublethal antibiotics on gut bacterial persistence and transmission*

Antibiotics induce large changes in the composition of the gut microbiome even at sublethal concentrations, by mechanisms that have remained elusive. Using larval zebrafish, which allow controlled studies of microbial dynamics, we found that sublethal doses of the common antibiotic ciprofloxacin cause severe drops in bacterial abundance. Contrary to conventional expectations, disruption was more pronounced for slow-growing, aggregated bacteria than for fast-growing, motile species. Three-dimensional live imaging revealed that antibiotic treatment promoted physical aggregation of bacteria in both planktonic and cohesive species and increased susceptibility to intestinal expulsion. Intestinal mechanics therefore amplify antibiotics effects on resident bacteria. A biophysical model, reminiscent of models of polymer growth and gelation, describes microbial dynamics and makes testable predictions of aggregation properties. The antibiotic-induced expulsion of live bacteria from the host influences the transmission of microbes to new hosts, which we suggest may contribute to the spread of antibiotic resistance.