Association of Diet and Antimicrobial Resistance in Healthy US Adults

OBJECTIVES: Antimicrobial resistance (AMR) represents a significant source of morbidity and mortality worldwide, with expectations that AMR-associated consequences will continue to worsen throughout the coming decades. Since resistance to antibiotics is encoded in the microbiome, interventions aimed at altering the taxonomic composition of the gut might allow us to prophylactically engineer microbiomes that harbor less antibiotic resistant genes (ARGs). Diet is one method of intervention, yet little is known about the association between diet and antimicrobial resistance. Our primary hypothesis was that increased intake of dietary fiber would be associated with reduced ARG abundance in human fecal metagenomes. Beyond our directed hypotheses, we utilized machine learning approaches on a variety of diet, physiological, and lifestyle features to assess whether the abundance of antibiotic genes is correlated with variables outside the scope of our directed hypotheses. METHODS: We examined diet using the food frequency questionnaire (FFQ, habitual diet) and 24-hour dietary recalls (ASA24) coupled with analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the USDA Nutritional Phenotyping Study. Additionally, we applied machine learning to examine 387 dietary, physiological, and lifestyle features for associations with antimicrobial resistance. RESULTS: We found that aminoglycosides were the most abundant and prevalent mechanism of AMR in these healthy adults and that aminoglycoside-o-phosphotransferases (aph3-dprime) negatively correlated with total calories and soluble fiber intake. Individuals in the lowest quartile of ARGs (Low-ARG) consumed significantly more fiber in their diets compared to Medium- and High-ARG individuals, which was concomitant with increased abundances of obligate anaerobes in their gut microbiota. CONCLUSIONS: Our results indicate individuals with lower abundances of antibiotic resistance genes consumed more diverse diets that were richer in fiber and limited in animal protein. We suspect that increased fiber likely drives the composition of the gut towards a more obligate anaerobe state, reducing footholds for facultative anaerobes, which are known harbors of inflammation and antibiotic resistance. FUNDING SOURCES: This research was supported by USDA-ARS grants.