Altered salivary miRNA profiles and microbiome composition correlate with psychosocial stress

Abstract

BackgroundPsychosocial stress is a risk factor for mental and physical illness. Previous studies have shown the potential of microRNAs (miRNAs) and the microbiome as biomarkers and/or mediators for stress responses. Here, we aimed to identify changes in these molecular markers in saliva samples from a cohort of 113 male police officers in service, stratified by stress response (SR) level (low, intermediate, and high), as a reference model for psychosocial stress. MethodsSalivary miRNome profiles and microbiome composition were analyzed by small RNA sequencing and shotgun metagenomics, respectively. SR-related miRNAs were identified with Docker4Seq and DESeq2 and functionally characterized using RBiomirGS. Differences in microbial communities among study groups were analyzed using MetaPhlAn, and microbial pathway prediction was performed with HUMAnN. A multi-omics integration of miRNA and microbial profiles was performed with the mixOmics framework. ResultsEighteen miRNAs were dysregulated (adj. p<0.05) between high- and low-SR groups and showed a progressive alteration from low- to high-SR groups. Functional enrichment analysis indicated that dysregulated miRNA targets were involved in apoptosis, cellular stress responses, and metabolic regulation. Despite limited shifts in oral microbial composition and diversity among the SR groups, the high-SR group showed a significant (adj. p<0.1) increase in microbial species involved in inositol degradation pathways, as well as a decrease in bacteria involved in L-tryptophan and thiamine biosynthesis, whose altered levels distinguished the high-SR group. ConclusionsSalivary miRNAs and oral microbiota may serve as non-invasive indicators of SR, helping to understand chronic psychosocial stress and cellular and behavioral responses. Plain language summaryPsychosocial stress is a major risk factor for mental and physical illness, with emerging evidence pointing to oral miRNAs and the microbiome as potential biomarkers. This study investigated stress-associated molecular changes in saliva from 113 male police officers stratified by perceived stress response (SR) into low, intermediate, or high responders. Eighteen miRNAs were dysregulated between high- and low-SR groups, whose target genes were involved in apoptosis, cellular stress responses, and metabolic regulation. Despite limited shifts in microbial populations, a functional analysis indicated increased taxa involved in inositol degradation and reduced taxa involved in L-tryptophan and thiamine biosynthesis, distinguishing high-SR individuals. These findings suggest that salivary miRNAs and microbiota may serve as non-invasive indicators of psychosocial stress, whose altered levels could reflect different SR.