Impact of pig farming activities on the gut microbiome and resistome of farmers: insights from metagenomics and Escherichia coli genomics

Abstract

Intensive swine production entails high antimicrobial use and close human–animal microbial exchange, with potential to remodel the human gut ecosystem and promote cross-host antimicrobial resistance (AMR) transmission. To quantify the impact of occupational exposure on the human gut microbiome and resistome, and to resolve putative livestock-to-human gene flow, we sampled feces from 103 swine farms in Sichuan, China. We generated metagenomes for 431 samples (farmers = 96, residents = 97, pigs = 238) and cultured 833 Escherichia coli isolates (farmers = 80, residents = 88, pigs = 665). Relative to unexposed residents, farmers exhibited reduced gut α-diversity and lower Gut Microbiome Health Index (GMHI). Taxonomic and functional profiles differed between farmers and residents, with farmers showing reduced abundances of several fiber-degrading and short-chain fatty acid-producing taxa, together with increased abundances of taxa and pathways related to mucin-derived glycan utilization. The resistome displayed an exposure gradient (pigs > farmers > residents). Farmers were enriched for determinants corresponding to commonly used veterinary drug classes (e.g., florfenicol, quinolones, MLS, aminoglycosides), whereas β-lactam genes were proportionally lower. Mobile genetic element (MGE) analysis revealed a pig-centered plasmid reservoir: among 157,298 nonredundant plasmid contigs, 1,415 carried ARGs, with 83.1%/18.3%/3.9% enriched in pigs/farmers/residents; notably, 88.8% of farmer-enriched plasmid contigs were co-enriched in pigs and harbored clinically important genes such as optrA , cfr , and mcr-10.1 . ARG-bearing phages were rare (106/227,476) but predominantly pig-associated. E. coli genomics indicated limited cross-host clonal transmission (five pig–farmer and one pig–resident events) yet higher ARG burdens in pig and farmer isolates. A random-forest classifier based on metagenomic taxonomic profiles distinguished farmers from residents (AUC = 0.921; specificity = 0.9; sensitivity = 0.775), nominating Schaalia odontolytica and Acinetobacter lwoffii as candidate exposure biomarkers. This study characterized the gut microbiome and resistome of pig-farm workers, non-farming residents, and pigs, revealing an association between occupational exposure to swine production and alterations in the gut microbiome and resistome of farmers. Shared ARG and plasmid-associated features suggest that MGEs may contribute to resistome overlap at the livestock–human interface, although the mechanisms of exchange require validation through longitudinal, environment-integrated, and strain-resolved studies. Overall, these results provide a basis for future One Health investigations of microbial and ARG sharing at the livestock–human interface. Video Abstract