Feng Xiangru, Zhong Jiaqian, Wang Jiaming, Lu Xiaoxuan, Chen Yijia, Yao Yanying, Ji Xiaoguo, Zhao Mengyao, Jin Jiayang, Li Juan, Zhao Liming
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China.
Department of Nutrition, Changzheng Hospital, Naval Medical University, Shanghai, China.
Brain Behav Immun. 2025 Nov;130:106114. doi: 10.1016/j.bbi.2025.106114. Epub 2025 Sep 19.
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.
密闭环境中的慢性应激会扰乱微生物群-肠-脑轴。然而，在密闭环境中社交和基本活动受限的人群（SRBARC）中，其特征性的微生物和代谢改变仍不清楚。本研究综合评估了情绪状态、肠道微生物群和代谢组学谱，以研究它们在SRBARC中的相互关系，旨在识别特征性微生物和代谢物。结果表明，SRBARC倾向于表现出抑郁/焦虑样行为，伴有下丘脑-垂体-肾上腺（HPA）轴激活、睾酮抑制和促炎细胞因子升高。全长16S rDNA测序分析表明，SRBARC的肠道微生物群中香农指数和Chao1指数较低。随机森林分析结合双队列验证表明，马西利亚布劳特氏菌、韦氏布劳特氏菌、共生粪球菌、普拉梭菌和毛螺菌科细菌可能是具有诊断价值的特征性微生物（发现队列AUC = 0.836，验证队列AUC = 0.840）。对粪便、血清和尿液的代谢组学分析揭示了SRBARC中氨基酸代谢的改变以及四氢生物蝶呤（BH4）合成的破坏，这影响了血清素（5-HT）和多巴胺（DA）途径。包括5-甲氧基色醇在内的四种代谢物被确定为可能与情绪状态相关的代谢物。这些特征性微生物和代谢特征与神经炎症和免疫相关，它们的相互作用可能在调节SRBARC的情绪状态中起关键作用。总之，本研究表明SRBARC的肠道微生物群、神经递质代谢和情绪状态之间存在潜在的相互作用，识别出了潜在的关键微生物特征和代谢物，这可能为制定基于肠道微生物群的干预策略提供理论基础。
