Tuesday, 14 April 2026

Fernández-de-Bobadilla, M.D., Pérez-Cobas, A.E., Andremont, A., Martínez, J.L., Baquero, F., Lanza, V.F., Coque, T.M... 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

Microbiome . 2026

"The findings challenge the idea of completely pristine human microbiomes and reveal the susceptibility of low-impact human populations to rapid acquisition of antimicrobial resistance following healthcare exposure" Dra. Teresa M. Coque

Summary:

Background: Metagenomics enables detailed profiling of genes encoding antimicrobial resistance. However, most studies focus exclusively on antibiotic resistance genes (ARGs), excluding those associated with non-antibiotic antimicrobials (metals, biocides), and often rely on methods with low-sensitivity and low-specificity. Furthermore, they rarely examine populations exposed to 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 8667 genes, including ARGs, metal resistance genes (MRGs) and biocide resistance genes (BRGs) (PMID: 29335005). Resistome profiles were compared with those of Europeans to assess population-level differences.

Results: ARG richness was similar between groups (259 in Wayampi vs. 264 in Europeans, 159 shared), but MRGs + BRGs gene richness was significantly higher in Wayampi (11,930 vs. 7419). Most genes appeared in a minority of individuals (mean 5% for ARGs, 2% for MRGs + BRGs), 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 in both groups, 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 distinguished cohorts based on ARG profiles (p < 0.001), but not on MRGs or BRGs. Correlation analysis revealed conserved gene-sharing networks and introgression of acquired ARGs and MRGs within both gut microbiomes.

Conclusions: The diverse and balanced Wayampi resistome reflects 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 gene distribution suggests varying levels of conserved gene sharing highways among populations, likely shaped by long-term microbial-human evolution, and supports a broader view on acquired antimicrobial resistance.

What are the main findings or key aspects of the work?

This study provides the most comprehensive characterization to date of antibiotic and non-antibiotic resistance gene pools in the human gut microbiome, using the Wayampi, a unique Indigenous population living in a minimally industrialized environment but chronically exposed to mercury pollution originating from artisanal gold mining, a pervasive widespread activity across in the Amazon with documented impacts on human health and food-chain contamination. Despite limited exposure to antibiotics, the Wayampi gut microbiome harbors a robust background resistome composed of acquired antimicrobial resistance genes (antibiotic, metal and biocide) that are shared with Western populations. This finding demonstrates that antimicrobial resistance is an ancient and conserved feature of the human gut microbiome rather than solely a by-product of human activities.

The study further reveals population-specific differences in resistance gene distributions that reflect ecological and taxonomic variation in microbiome structure. Notably, the rapid emergence of clinically relevant resistance genes following healthcare or antibiotic exposure highlights the resistome as a "robust-yet-fragile" ecogenetic system, susceptible to disruption through the introduction of key mobile genetic elements. Importantly, the comprehensive detection of resistance genes was enabled by targeted, high-resolution metagenomic approaches such as ResCap (an original design previously developed by the authors, PMID: 29335005), which allow simultaneous screening of antibiotic resistance genes as well as antimicrobial resistance determinants to metals and biocides, many of which remain underexplored in standard metagenomic surveys.

What are the key implications of this work for science and/or society?

Scientific implications. This study reframes the human gut resistome as a scale-free ecological network centered on a conserved core of highly connected resistance genes that facilitate gene exchange among microbes. By encompassing resistance to antibiotics, metals, and biocides, it expands current resistome paradigms and emphasizes the role of multiple antimicrobial pressures in driving resistance evolution. High-resolution capture-based methods demonstrate the value of sensitive tools capable of detecting not only antibiotic resistance genes but also metal and biocide determinants, which may promote co-selection and long-term persistence of resistance.

Societal and public health implications. The findings challenge the idea of completely pristine human microbiomes and reveal the susceptibility of low-impact Indigenous populations to rapid acquisition of antimicrobial resistance following healthcare exposure. These results underscore the need for next-generation, integrated surveillance strategies that extend beyond antibiotics alone and support One Health frameworks linking human health, environmental contamination, and microbial evolution to address the global antimicrobial resistance crisis.