A Roadmap of The Human Body Resistome

Abstract

BackgroundIn response to the global antibiotic resistance crisis, efforts have been focused on gaining a better understanding of resistomes (sets of antibiotic resistance genes (ARGs)) and the dispersion of ARGs in nature. A comprehensive metagenomic characterization of the human body resistome is paramount for laying the foundation to develop a better strategy to address this health concern. Here, we study the resistomes of 771 samples from five major body parts of healthy subjects from the Human Microbiome Project (HMP). In line with the One Health concept (WHO), we also investigated the presence of ARGs from the HMP in 272 pristine environments. ResultsOf all the detected HMP genes/proteins (9.17E+07), 40,816 were ARGs showing high interindividual and inter-body-site abundance variability. Nares had the highest ARG abundance (2.18±2.64 ARGs/Mb; ≈5.5 ARG per bacterial genome), while the gut (0.34±0.34 ARGs/Mb; ≈1.3 ARG per bacterial genome), which also showed the highest richness of different ARG types, had the lowest abundance. Fluroquinolone resistance genes were the most abundant antibiotic resistance gene family, followed by MLS or tetracycline resistance genes, depending on the body site. From all the detected ARGs, we found 366 different ARG types, with parC R (fluoroquinolone resistance) being the most abundant in the oral cavity, mprF (peptide antibiotic resistance) in the skin and nares, and tetQ (tetracycline resistance) in the gut and vagina. Most of the ARGs belonged to common bacterial commensals, and many of them were also multidrug resistance genes and were more abundant in the nares and vagina. The total number of ARGs from the HMP data (n=34) detected in pristine environments (266 samples) was negligible, and most of them (73%) were classified as housekeeping genes in autochthonous bacteria having known mutations conferring antibiotic resistance (natural reservoirs). A significant fraction of ARGs (24%) in pristine environments were actually from exogenous contaminants. The detection of identical HMP ARGs in autochthonous bacteria was extremely infrequent (3%). Conclusions Our results comprehensively reveal the resistomes from all body parts and HMP samples that can serve as a baseline for comparison for long-term survey and monitoring of human resistome variations. Finally, our data provide hope, since the spread of common ARGs from the HMP data to pristine environments thus far remains very unlikely.