Each person's gut microbiome contains a specific community of microorganisms that normally remains stable for years. However, it can be thrown off balance by factors such as dietary changes, infections or medications. Antibiotics in particular have a strong influence on the microbiome. In response, microorganisms employ various resistance mechanisms, with individual bacterial populations evolving through selection of antibiotic-resistant variants. Yet, the extent and mechanisms of these processes and their impact on the ecology of the microbial community are poorly understood.

In a comprehensive metagenomic study, scientists investigated the evolution of intestinal bacteria exposed to repeated disruptions by antibiotics. For this purpose, they used a gnotobiotic mouse model, i.e., mice kept germ-free and stably colonised with a known consortium of bacteria. This model allows evolutionary studies of individual members of the community in the natural host under well-defined and controllable conditions.

The researchers then analysed the effects of different classes of antibiotics on the microbiome over a period of 80 days. Using metagenomic analyses, they followed the selection of putative antibiotic resistance-promoting mutations in the bacterial populations, and subsequently analysed the characteristics of evolved bacterial clones isolated from the communities.

"We were able to track how repeated antibiotic therapy leads to the selection of antibiotic-resistant commensal bacteria, which after a while increases the resilience of the microbial community to certain antibiotics such as the tetracyclines. In addition to adaptation of the microbiome through evolution of individual microorganisms, we also found evidence of resistance development of individual bacteria through slowing of cell growth. The microbiome adapts to the treatment, so to speak, and is better able to withstand it," says the senior author.

In addition, the research team observed an induction of prophages triggered by treatment with certain antibiotics. In this process, lysogenic bacteriophages—whose genomes are integrated into bacterial genomes—are activated, whereupon they proliferate and lyse the host cells upon release of new viral particles. "This is an example of how antibiotics can also indirectly affect bacterial survival," says the first author of the study.

Overall, the study shows an immense diversity in the response of the microbiome to antibiotic treatments. This includes, for example, ecological effects such as the inhibition of a microorganism by the elimination of an important "partner" bacterium in the metabolic network of the gut ecosystem.

https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(23)00206-8