Kerwyn C Huang

– Abstract –

Resilience of the Gut Microbiota to Perturbations

The use of antibiotics to resolve bacterial infections has saved countless lives since the discovery of sulfa drugs nearly a century ago. Unfortunately, the overzealous and often inappropriate prescription of antibiotics has led to a rise in antibiotic resistance and has wide-ranging effects on the communities of commensal bacteria that live on and within the host. Antibiotic perturbation alters the composition and function of these communities and increases susceptibility to future infection, underscoring the need to design antibiotics that target pathogens and minimize damage to commensals. In previous efforts to understand how antibiotics affect communities of commensal bacteria, antibiotic sensitivity has been studied in pure cultures of individual bacteria grown in laboratory media. These in vitro results are not always mirrored in studies of clinical and animal models, which comprise a body of literature that is in and of itself also contradictory and inconsistent. Understanding the factors that underlie a bacteria’s response to antibiotics within a complex host-associated community will require integration of in vitro and in vivo data and careful dissection of quantifiable aspects of the host environment and community. We show that the gut microbiota has a robust response to antibiotic perturbation, even after a massive 105-fold drop in bacterial load, showing recovery during antibiotic treatment in a housing-dependent manner. The coarse-grained taxonomic kinetics of this recovery are relatively independent of the microbiota context, the antibiotic target, multiple antibiotic treatments, or dietary shifts, although dietary shifts result in a much larger perturbation to the bacterial load. We also show that the recovery is dominated by a few species, and the final state after stabilization exhibits signs of substantial extinction that are not predictable based on in vitro growth in pure culture. These results highlight the importance of community context in the sensitivity of bacteria to antibiotics by modulating the initial composition of the microbiota in humanized mice through diet and multiple rounds of antibiotics.