Colonization and evolution after antibiotic perturbation in the human gut microbiome
Authors: Katherine Xue; Doran Goldman; Kerwyn Huang; Dmitri Petrov; Benjamin Good; David Relman
Affiliation: Stanford University
Keywords: Experimental evolution
Gut commensal bacteria frequently form long-term associations with human hosts but can also transmit between hosts to colonize new microbial communities. The ecological context and evolutionary pressures associated with strain colonization and transmission remain largely unknown, despite their importance for designing successful targeted microbiome therapeutics. Here, we investigate the dynamics of strain transmission and evolution in a longitudinal household cohort of 48 healthy adults from 22 households over two months, during which one subject in each household took a 5-day course of the antibiotic, ciprofloxacin. Prior work has shown that cohabiting individuals frequently carry closely related microbial strains, suggesting that households are sites of natural microbial transmission. We developed methods to identify strain transmission events in our study using metagenomic sequencing data, and we tracked the ecological context and evolutionary dynamics of these transmission events in our household cohort. Individuals had heterogeneous ecological responses to antibiotic perturbation: in some subjects, the gut microbiome rapidly returned to its initial composition after antibiotic exposure, but in others, the microbiome transitioned after antibiotic exposure to an alternative stable state that persisted through months of follow-up sampling. In one intriguing case of a subject who experienced a major antibiotic perturbation, a strain of Bacteroides stercoris transmitted from a cohabiting partner after antibiotics and maintained a relative abundance of more than 50 percent through a year of subsequent follow-up sampling, suggesting that, in some cases, strain transmission can play a major role in reshaping the post-antibiotic community. We are now working to identify mutations that arise in strains after transmission as they adapt to a new host context. Our work shows that colonization following antibiotic perturbations can substantially remodel gut microbial communities and helps shed light on the evolutionary pressures that gut microbes experience as they circulate and transmit between hosts.