Dietary impact on the gut resistome: western diet independently increases the prevalence of antibiotic resistance genes within the gut microbiota.

Approximately half of surgical site infections are caused by pathogens resistant to the antibiotics used for prophylaxis. We recently demonstrated that when mice are fed a western diet (WD) that is high in fat and low in fiber, exposed to antibiotics, and undergo an otherwise recoverable surgery, they develop lethal sepsis associated with dissemination of multi-drug-resistant pathogens. Here, we hypothesized that a WD alone can drive the intestinal microbiome to become populated by antibiotic-resistant bacteria independent of exposure to antibiotics. The cecal microbiota response to antibiotics was determined utilizing Biolog Phenotype Microarrays in the presence of 48 different antibiotics. WD-fed mice had a significant increase in antibiotic resistance within their microbiome compared to mice on a standard low-fat, high-fiber diet (SD) including aminoglycosides, tetracyclines, cephalosporins, fluoroquinolones, and sulfamethoxazole. By metagenomic sequencing, there was an increase in the antibiotic resistance genes (ARGs) within the WD cecal microbiota, including CfxA2, ErmG, TetQ, and LnuC. After just 7 days of WD, the ARGs ErmG and CfxA2 were detectable within the stool. WD independent of antibiotic exposure increases the presence of ARGs within the gut microbiota independent of antibiotic exposure.IMPORTANCEAntibiotic resistance is a major challenge in healthcare and results in significant morbidity and mortality. Currently, half of surgical site infections are caused by pathogens resistant to antibiotics used for prophylaxis. In this study, we demonstrate that a western diet alone has the ability to increase the presence of antibiotic resistance genes within the gut microbiome. By understanding dietary influences on the gut resistome, we may improve our understanding of infections with antibiotic-resistant organisms and one day develop personalized antibiotic regimens based on an individual's gut resistome.