Description
- Abstract:
- Antibiotic-induced gut dysbiosis is currently a frequent and serious side effect of antibiotic use. Host diet can be a therapeutic target to modulate the structure and function of the microbiome during antibiotic treatment. In this study, we utilize metagenomic and metatranscriptomic sequencing combined with de novo gene assembly to elucidate changes to the microbiome during diet modulation. Using a murine model, we found that supplementation of fiber prebiotics alleviates the dysbiotic effect of antibiotics, increasing microbial diversity post-antibiotics. Conversely, glucose supplementation exacerbated the dysbiotic effects of antibiotics. We observe transcriptional signatures of high-energy metabolism in glucose supplemented mice compared to fiber-supplemented mice. Glucose led to metabolic reactions with higher redox potential along with increased expression of oxygen radical chelating reactions. Transcriptional activity of high energy electron transfers and increased expression of Complex 1 associated bacteria was observed. This suggests that dietary carbon source can affect the energetic environment of the gut leading to selection of higher energy electron acceptors such as oxygen and nitrate. Further, we characterize the chemical redox environment by using electrochemical techniques to measure the oxidation-reduction potential (ORP) of the gut post diet and antibiotic disruption. Antibiotics increase the ORP of the gut, however this increase is suppressed when on a fiber diet and exacerbated on a glucose diet. This indicates that fiber prebiotics modulate bacterial metabolism in the gut by selecting for low-energy metabolic reactions which can protect these microbes during antibiotic treatment. We also show that inhibiting ETC proteins involved in higher energy metabolism such as complex 1 was able to protect gut microbes from the increase in redox potential associated with glucose. This transformative research could aid efforts to decrease damage to the microbiome from antibiotics and provide an avenue for fiber therapeutics.
- Notes:
- Thesis (Ph. D.)--Brown University, 2023
Citation
Penumutchu, Swathi,
"Protecting from Antibiotic-Induced Gut Microbiome Dysbiosis by Modulating redox Metabolism"
(2023).
Pathobiology Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://repository.library.brown.edu/studio/item/bdr:jjy2rtkp/
