Advisor: 

Kostas Konstantinidis, Ph.D. (School of Civil and Environmental Engineering, Georgia Tech)

Committee Members:

Kostas Konstantinidis, Ph.D. (School of Civil and Environmental Engineering, Georgia Tech)

Michael Woodworth, MD (Division of Infectious Diseases, Emory University)

Edward Botchwey, Ph.D. (School of Biomedical Engineering, Georgia Tech)

Identifying a potential consortium of bacterial species and functions for the reduction of enteric multidrug resistant organisms by microbiota transplantation

Antibiotic resistance is an urgent healthcare crisis. Traditional drug development is not able to keep up with the evolution of new resistant pathogens, leaving very few viable therapeutic options. Faecal microbiota transplantation (FMT) has shown remarkable promise in its success in preventing recurrent Clostridioides difficile infections (rCDI), with a success rate of up to 90% and the approval of two commercial products since 2022. FMT success in rCDI is often accompanied by significant shifts in the composition of antibiotic resistance genes of patients’ gut microbiomes, but studies evaluating the direct effect of FMT in treating multidrug resistant organisms (MDROs) have been met with mixed results. Success rates vary between studies, scalability and safety of FMT are ongoing challenges, and no consensus on the key bacterial taxa involved in successful applications has been reached, likely due to the high inter-individual heterogeneity of the human gut microbiome and the complex diversity of MDROs. Additionally, there is a lack of functional analysis to explain the mechanism behind successful FMT treatments. In this study, we use a temporal definition of engraftment and identify a consortium of fourteen bacterial species that are engrafting across different studies and are negatively correlated with pathogen abundance. This consortium differs from the taxa responsible for rCDI prevention, which has important implications for future drug development. We also identify gene functions that may facilitate the engraftment of these taxa, as engrafting genes are involved in growth, adhesion and environmental sensing. Overall, we show that our bioinformatic approach can identify a consensus in taxonomic and functional changes after FMT and could be adapted to other microbiota-responsive indications. Here, we apply our approach to efficiently nominate candidate strains to reduce MDRO colonisation and address the global threat of antibiotic resistance.