Dietary and Microbial Strategies to Suppress Antibiotic-Induced AMR in the Gut Microbiome

About This Grant

PROJECT SUMMARY Antimicrobial resistance (AMR) constitutes a global health crisis, directly linked to significant mortality and healthcare costs. Antibiotics, crucial in treating infections, profoundly disrupt the gut microbiome, depleting natural defenses and facilitating the proliferation of resistant pathogens. Such disruptions disproportionately affect vulnerable populations like hematopoietic cell transplant (HCT) patients, significantly increasing their risk of life-threatening infections such as bacteremia. Thus, there is an urgent unmet need for targeted, microbiome- preserving interventions to limit AMR spread and enhance patient outcomes. This project leverages a uniquely detailed, longitudinal dataset comprising over 9,000 meticulously documented meals consumed during the hospital stays of 170 HCT patients to unravel complex interactions among antibiotics, dietary components, and microbiome dynamics. Preliminary data indicate that diets rich in sweets, including sugary beverages and high-sugar nutritional supplements commonly administered in clinical settings, could exacerbate antibiotic-induced microbiome disturbances. Encouragingly, however, certain high- sugar nutritional supplements deviated from this general detrimental trend of dietary sweets, providing evidence that specific dietary compositions or complete meals may support microbiome resilience. Indeed, mouse experiments have shown that diet more so than fecal transplants can mediate microbiome damage from antibiotics. We propose a rigorous, two-pronged approach to uncover dietary strategies that promote microbiome resilience and recovery and suppress AMR pathogen proliferation. Aim 1 will systematically identify specific meals and dietary components that either alleviate or worsen antibiotic-induced microbiome damage using advanced Bayesian analysis of our unprecedented antibiotic-microbiome-diet dataset, subsequently validating these findings through controlled mouse experiments. Aim 2 will employ genome-scale modeling and experimental validation to dissect genetic mechanisms by which sugar-rich diets enhance the growth and persistence of AMR pathogens. By pinpointing precise genetic determinants influencing microbial fitness under dietary perturbation, this work will guide targeted therapeutic strategies. Ultimately, the project aims to generate actionable, evidence-based dietary guidelines that safeguard the microbiome, minimize AMR expansion, and improve clinical outcomes for immunocompromised patients. The proposed study strategically bridges fundamental microbial ecology with clinical translation, offering a cost- effective, immediate, and broadly applicable solution to mitigate AMR’s global health impact.