Oxygen and Metabolism: Digesting Determinants of Antibiotic Susceptibility in the Gut

Microbial metabolism is a major determinant of antibiotic susceptibility. Environmental conditions that modify metabolism, notably oxygen availability and redox potential, can directly fine-tune susceptibility to antibiotics. Despite this, relatively few studies have discussed these modifications within the gastrointestinal tract and their implication on in vivo drug activity and the off-target effects of antibiotics in the gut. In this review, we discuss the environmental and biogeographical complexity of the gastrointestinal tract in regard to oxygen availability and redox potential, addressing how the heterogeneity of gut microhabitats may modify antibiotic activity in vivo. We contextualize the current literature surrounding oxygen availability and antibiotic efficacy and discuss empirical treatments. We end by discussing predicted patterns of antibiotic activity in prominent microbiome taxa, given gut heterogeneity, oxygen availability, and polymicrobial interactions. We also propose additional work required to fully elucidate the role of oxygen metabolism on antibiotic susceptibility in the context of the gut.