Association of diet and antimicrobial resistance in healthy U.S. adults

Authors: OLIVER, ANDREW - Oak Ridge Institute For Science And Education (ORISE); XUE, ZHENGYAO - University Of California, Davis; VILLANUEVA, YIRUI - University Of California, Davis; DURBIN-JOHNSON, BLYTHE - University Of California, Davis; Alkan, Zeynep; TAFT, DIANA - University Of California, Davis; LIU, JINXIN - Nanjing Agricultural University; KORF, IAN - University Of California, Davis; Laugero, Kevin; Stephensen, Charles; MILLS, DAVID - University Of California, Davis; Kable, Mary; Lemay, Danielle

Submitted to: mBio
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/14/2022
Publication Date: 5/10/2022
Citation: Oliver, A., Xue, Z., Villanueva, Y.T., Durbin-Johnson, B., Alkan, Z., Taft, D.H., Liu, J., Korf, I., Laugero, K.D., Stephensen, C.B., Mills, D.A., Kable, M.E., Lemay, D.G. 2022. Association of diet and antimicrobial resistance in healthy U.S. adults. mBio. 13(3). Article e00101-22. https://doi.org/10.1128/mbio.00101-22.
DOI: https://doi.org/10.1128/mbio.00101-22

Interpretive Summary: Antimicrobial resistance (AMR) represents a major burden to healthcare systems worldwide, with the public health community largely in consensus that AMR will be a major cause of death worldwide in the coming decades. Humans carry resistance in the microbes that live in and on us, collectively known as the human microbiome. Diet is a powerful method for shaping the human gut microbiome and may be a tractable method for lessening antibiotic resistance at the population scale, yet little is known about the relationship between diet and antimicrobial resistance. We examined this relationship in healthy individuals with varying amounts of antibiotic resistance, and found that individuals who consumed diverse diets, high in fiber and low in animal protein had lower amounts of antibiotic resistance. Our results suggest dietary interventions may be useful in lessening the burden of antimicrobial resistance and may ultimately motivate future dietary guidelines which will consider how nutrition can reduce the impact of infectious disease.

Technical Abstract: 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. To address this knowledge gap, 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. 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, especially from the family Clostridiaceae, in their gut microbiota. Finally, we applied machine learning to examine 387 dietary, physiological, and lifestyle features for associations with antimicrobial resistances, finding that increased phylogenetic diversity of diet was associated with Low-ARG individuals. These data suggest diet may be a potential method for reducing the burden of AMR.