Occupational environments are associated with distinct oral and gut microbiome–metabolome profiles

The profound health impacts of distinct long-term work environments, such as indoor sedentary versus outdoor physical labor, remain poorly understood at the microbial and metabolic levels. To address this, we used an integrated metagenomic and metabolomic approach to systematically compare the oral and gut ecosystems of indoor sedentary workers (university teachers) and outdoor physical laborers (construction and transportation workers). Our analysis revealed stark, niche-specific differences. Outdoor laborers showed higher salivary microbial diversity, whereas indoor workers had higher gut microbial diversity coupled with a marked reduction in microbial resistance genes. Crucially, statistical mediation analysis of the ‘environment-microbiome-metabolite’ axis uncovered fundamentally different regulatory logics in the two niches. The oral ecosystem operated on a ‘push-and-pull’ model of mixed mediation; notably, the indoor sedentary lifestyle was positively associated with the key metabolic risk marker, uric acid, statistically mediated by a reduced abundance of purine-competing Prevotella species. In contrast, the gut ecosystem displayed a highly uniform ‘many-to-one’ architecture, where diverse microbial shifts converged to statistically mediate a reduction in a small set of metabolites, primarily a single exogenous steroid derivative. Furthermore, these multi-omics signatures were highly predictive, with salivary metabolome data distinguishing the two groups with up to 98.04% accuracy. This study suggests that multi-omics profiles may serve as a sensitive ‘biological archive’ of an individual’s work environment. These highly predictive signatures are promising candidates for biomarker development in health monitoring and forensic inference, and highlight potential microbe-metabolite targets for future intervention studies tailored to lifestyle-specific risks.