Chronic stress in confined environments can disrupt the microbiota-gut-brain axis. However, the characteristic microbial and metabolic alterations in socially and radically basic activity-restricted people in confined environments (SRBARC) remain unclear. This study integrated assessments of emotional states, gut microbiota, and metabolomic profiles to investigate theirinterrelationships in SRBARC, aiming to identify characteristic microbes and metabolites. The results suggested that the SRBARC tend to exhibit depressive/anxiety-like behaviors, accompanied by hypothalamic-pituitary-adrenal (HPA) axis activation, suppressed testosterone, and elevated pro-inflammatory cytokines. Full-length 16S rDNA sequencing analysis indicated lower Shannon and Chao1 indices in the gut microbiota of the SRBARC. Random forest analysis combined with dual-cohort verification suggested that Blautia massiliensis, Blautia wexlerae, Coprococcus comes, Faecalibacterium prausnitzii, and Lachnospiraceae bacterium may serve as characteristic microbes with diagnostic value (discovery cohort AUC = 0.836, validation cohort AUC = 0.840). Metabolomic analysis of feces, serum and urine revealed alterations in amino acid metabolism and disruptions in tetrahydrobiopterin (BH4) synthesis in the SRBARC, which affected serotonin (5-HT) and dopamine (DA) pathways. Four metabolites, including 5-methoxytryptophol, were identified as potentially metabolites associated with emotional states. These characteristic microorganisms and metabolic features were associated with neuroinflammation and immunity, and their interactions may play a key role in regulating emotional states in SRBARC. In summary, this study suggested a potential interplay among gut microbiota, neurotransmitter metabolism, and emotional states in the SRBARC, identifying potential key microbial signatures and metabolites that may provide a theoretical foundation for developing gut microbiota-based intervention strategies.
Gut-Brain Axis