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.

Grant Number: 1R56AT012463-01A1
NIH Institute/Center: NIH
Principal Investigator: Peter Belenky