The Antimicrobial Gut Resistome of the Wayampi reveals a shared background of antibiotic and metal resistance genes with industrialized populations, underscoring the “robust-yet-fragile” architecture of human gut microbiomes

Background. Antimicrobial resistance (AR) is a global health challenge that requires a OneHealth perspective to identify hotspots and mitigate transmission. Metagenomics enables the comprehensive analysis of AR gene pools in microbiomes. Still, most studies are restricted to antibiotic resistance genes (ARGs), use limited sensitivity and specificity methods, and scarcely analyze pristine populations. Here, we deeply analyze the fecal resistomes of 87 Wayampiis, an Amerindian human population in a remote geographical community of French Guiana with gold-mining activities, using targeted metagenomics based on last-generation in-solution capture platforms (PMID: 29335005). For the first time, we extended the analysis to other resistance genes beyond ARGs, biocide resistance genes (BRGs), and metal resistance genes (MRGs)). Results. The Amerindians' gut resistome (ARGs, MRGs, BRGs) are similar to those of Europeans. Still, they differ in the gene composition of all gene categories, with gene evenness significantly different for ARGs and BRGs. We also provide a friendly interface to analyze resistomes using the ResCap tool. Conclusions. The antimicrobial resistome of Wayampiis confirms how ecology and phylogeny determine the gene pools. It also highlights the impact of the environment in the emergence and evolution of antimicrobial resistance genes with metal pollution becoming a relevant selective pressure through the food web. Moreover, the number of mobile core or highly abundant and redundant ARGs and MRGs suggest the carriage of mobile genetic elements ready to acquire and rapidly spread novel genes in pristine populations. Finally, the analysis of the metalome is necessary to explore background and baseline antimicrobial resistomes and accurately identify hotspots, mitigate transmission.