Alleviating antibiotic-induced microbiome dysfunction by quenching the microbial redox environment

PROJECT SUMMARY Antibiotic-induced disruption (AID) of the gut microbiome can lead to severe conditions like C. diff colitis and may contribute to long-term health issues, including obesity and diabetes. There is an urgent need to develop interventions that mitigate these negative impacts while preserving the antibiotics' effectiveness. Our preliminary

data suggest that dietary fiber reduces antibiotic disruption by decreasing the gut's redox potential, which in turn favors a low-energy, fermentative metabolic environment. This environment protects core microbiome members by reducing their metabolic rate and ATP production, which are linked to antibiotic susceptibility. In Aim 1, we

will use an ex vivo microbiome culture approach to test endogenous redox sinks and small molecule regulators of bacterial redox as modulators of AID and determine the influence of these modulators on microbiome resilience, recovery, and pathobiont susceptibility. This research aims to identify mechanisms that can be

translated into therapies for protecting the microbiome during antibiotic treatment, particularly for vulnerable populations.