Gut microbiome resistotypes reflect chronological age and Enterobacteriaceae relative abundance

Surveillance of antibiotic resistance genes (ARGs) in the human gut microbiota is critical for informing public health interventions and antibiotic stewardship strategies, taking into account sociodemographic, behavioral, and health-related factors. Although metagenomics research has grown exponentially, few studies have described resistome dynamics over time. In this study, we investigated resistome profiles over a 5-year interval (between 2016-2017 and 2022) in adult residents of Arkhangelsk, Northwestern Russia.

Over 5 years, we observed an increase in ARGs richness and abundance along with the prevalence changes in genes conferring resistance to aminoglycosides (aph2, aph3, ant9), lincosamides (lnuC), chloramphenicol (cat, catA), and macrolides (ermG, ermB). We have identified two resistotypes in our data that differed in the number of identified ARGs. The less frequent resistotype 2, characterized by a higher number of ARGs, was associated with higher participants' chronological age and increased Enterobacteriaceae abundance. Approximately one-third of the participants have shifted from one resistotype to another within a 5-year period. Temporal changes in resistome profiles occurred unevenly among participants, with the greatest changes noted for 41-45 and 61-65 age groups. No associations were found between COVID-19 history and resistome composition.

We showed an increase in overall ARG richness, ARG abundance, and the prevalence of certain ARGs in microbiomes of adult residents of Arkhangelsk over a 5-year period. We have identified two resistotypes; the one with higher ARGs richness was linked to higher chronological age and Enterobacteriaceae family relative abundance. These findings underscore the necessity for further antibiotic resistance surveillance to address the accelerating global dissemination of ARGs, while highlighting age as an underrecognized factor contributing to resistome dynamics.