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.

ARG richness was similar between Wayampi and European populations, with a substantial number of shared genes.

• ARG richness was 259 in Wayampi vs. 264 in Europeans, with 159 genes shared between groups.
• The study analyzed fecal resistomes of 95 Wayampi individuals using a targeted metagenomic capture platform covering 8667 genes.
• The capture platform included ARGs, metal resistance genes (MRGs), and biocide resistance genes (BRGs).

Metal resistance genes and biocide resistance genes combined were significantly more abundant in the Wayampi than in Europeans.

• MRGs + BRGs gene richness was 11,930 in Wayampi vs. 7,419 in Europeans.
• This difference was described as statistically significant.
• Copper and arsenic resistance genes predominated in both groups, followed by those for zinc, iron, cobalt, and nickel.

Most resistance genes appeared in only a minority of individuals, but several specific ARGs were universally present across all individuals in both populations.

• The mean prevalence of ARGs was 5% per individual, and 2% for MRGs + BRGs.
• ARGs present in all individuals included tetracycline resistance genes tet(32), tet(40), tet(O), tet(Q), tet(W), tet(X), and tetAB(P).
• Universally shared aminoglycoside resistance genes included ant6'-I and aph3-III; macrolide resistance genes included ermB, ermF, and mefA; sulfonamide resistance gene sul2 was also universally present.
• Tetracycline resistance genes predominated overall across both populations.

Beta-lactam resistance genes were more common in Wayampi, while aminoglycoside, amphenicol, and folate inhibitor resistance genes were more frequent in Europeans.

• Beta-lactam resistance genes showed higher prevalence in the Wayampi cohort.
• Genes conferring resistance to aminoglycosides, amphenicols, and folate inhibitors were more frequent in Europeans.
• These compositional differences were identified despite similar overall ARG richness between the two populations.

A substantial proportion of Wayampi individuals carried acquired MRGs for copper, silver, arsenic, and mercury.

• Up to 76% of Wayampi individuals carried acquired MRGs.
• Specific MRG operons identified included pcoABCDRS and tcrB for copper, silACFPRS for silver, ars for arsenic, and mer for mercury detoxification.
• This finding is notable given the Wayampi are an Indigenous community in remote French Guiana with minimal anthropogenic pollution exposure.

Shannon diversity indices for ARGs, MRGs, and BRGs were similar between Wayampi and Europeans, but resistome composition and evenness differed significantly.

• Shannon diversity indices were similar for ARGs, MRGs, and BRGs across both cohorts.
• Composition and evenness differed significantly between the two populations.
• UMAP and ADONIS analyses distinguished cohorts based on ARG profiles (p < 0.001), but not on MRGs or BRGs profiles.

Correlation analysis revealed conserved gene-sharing networks and introgression of acquired ARGs and MRGs within both gut microbiomes.

• The analysis identified conserved gene-sharing networks present across both the Wayampi and European gut microbiomes.
• The resistome architecture was described as consistent with the 'robust-yet-fragile' architecture of scale-free networks.
• The distribution of genes was described as 'patchy yet resilient,' suggesting varying levels of conserved gene-sharing highways among populations.

The Wayampi resistome reflects a background of 'core' and 'shell' acquired ARGs and MRGs shared with industrialized populations, suggesting long-term microbial-human co-evolution.

• The diverse and balanced Wayampi resistome was interpreted as reflecting a less perturbed microbiome compared to industrialized populations.
• The patchy yet resilient gene distribution was attributed to 'long-term microbial-human evolution.'
• The findings support a broader view of acquired antimicrobial resistance beyond antibiotic exposure alone.
• The study used a targeted metagenomic capture platform (PMID: 29335005) covering 8667 genes, addressing limitations of low-sensitivity and low-specificity methods used in prior studies.