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

Background Metagenomics enables detailed profiling of antimicrobial resistance genes, but most studies focus solely on antibiotic resistance genes (ARGs), use low-sensitivity methods, and rarely investigate populations with minimal anthropogenic pollution. We analyzed fecal resistomes of 95 Wayampi individuals, an Indigenous community in remote French Guiana, using a targeted metagenomic capture platform covering 8,667 resistance genes to antibiotics (ARGs), metals (MRGs), and biocides (BRGs) (PMID: 29335005). Resistome profiles were compared with Europeans to assess population-level differences.

ARG richness was similar between groups (259 in Wayampi vs. 264 in Europeans, 159 shared), but MRGs + BRGs (BAC) gene richness was signifcantly higher in Wayampi (3,670 vs. 2,039). Most genes appeared in a minority of individuals (mean 5% for ARGs, 2% for BAC), but several ARGs for tetracyclines [tet(32), tet(40), tet(O), tet(Q), tet(W), tet(X), tetAB(P)], aminoglycosides (ant6′-I, aph3-III), macrolides (ermB, ermF, mefA), and sulfonamides (sul2) were present in all individuals. Tetracycline resistance genes predominated overall, while beta-lactam resistance genes were more common in Wayampi, and genes conferring resistance to aminoglycosides, amphenicols, and folate inhibitors were more frequent in Europeans. Among MRGs, copper and arsenic resistance genes prevailed, followed by those for zinc, iron, cobalt, and, nickel. Up to 76% of Wayampiis carried acquired MRGs for copper (pcoABCDRS and tcrB), silver (silACFPRS), arsenic (ars), and mercury (mer) detoxification. Shannon diversity indices were similar for ARGs, MRGs, and BRGs, but composition and evenness differed significantly. UMAP and ADONIS analyses distinguised cohorts by ARG profiles (p < 0.001), but not MRGs or BRGs. Correlation analysis revealed conserved gene-sharing networks and introgression of acquired ARGs and MRGs in both gut microbiomes.

The diverse and balanced Wayampi resistome reflect a less perturbed microbiome compared to industrialized populations, and reveals a background of core and shell acquired ARGs and MRGs, consistent with the “robust-yet-fragile” architecture of scale-free networks. The patchy yet resilient distribution of resistance genes reflects varying levels of conserved gene sharing highways probably shaped by long-term microbial-human evolution, and support a broader view of acquired antimicrobial resistance. Competing Interest Statement The authors have declared no competing interest.