No strain, no gain: within-host bacterial microdiversity and human health

It is well established that within a bacterial species, genotypic and phenotypic variation leads to differences in virulence, antibiotic susceptibility, and metabolism. However, there is also increasing evidence that often multiple variants of the same species co-inhabit the same site in the human body, both during health and disease. This within-host microdiversity can develop over time for pathogens in chronic infections and has been observed for many members of the microbiota, for instance in the gut and on the skin. Research is just beginning to uncover how this within-host intra-species diversity develops and why it matters. Intra-species diversity is largely stable over time, with occasional selective sweeps of new genotypes, and the overall level of diversity is modulated by both microbe-microbe and microbe-host interactions. Furthermore, data indicate that within-host microdiversity can impact the stability of bacterial communities, their antimicrobial resistance, and the efficacy of probiotics and microbiota transplants. Here, we describe the evolutionary and ecological processes that promote high or low within-host microdiversity and the extent of this diversity in the human microbiota and in infections. In addition, we consider how microdiversity within individuals shapes the functional role of the human microbiota and the progression of disease. Together, within-host microdiversity is a newly developing way to think about the diversity of human-associated microbes, with implications in how we treat chronic infections and manipulate our microbiota to promote health.