Wu Hui, Liu Yaxi, Han Yunwu, Liu Bingdong, Chen Shengyun, Ye Zhiye, Li Jianbo, Xie Liwei, Wu Xiaoli
Psychiatry Department, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Psychiatry Department, The First People's Hospital of Kashi, Sun Yat-sen University, Kashi, China.
Schizophr Bull Open. 2024 Oct 28;5(1):sgae026. doi: 10.1093/schizbullopen/sgae026. eCollection 2024 Jan.
Gut microbiota has been implicated in the pathogenesis of schizophrenia (SZ) and relevant changes in the brain, but the underlying mechanism remains elusive. This study aims to investigate the microbiota-gut-brain crosstalk centered on peripheral inflammation in SZ patients.
We recruited a cohort of 182 SZ patients and 120 healthy controls (HC). Multi-omics data, including fecal 16S rRNA, cytokine data, and neuroimaging data, were collected and synthesized for analysis. Multi-omics correlations and mediation analyses were utilized to determine the associations of gut microbiome with inflammatory cytokines and neuroimaging characteristics. Additionally, machine learning models for effective SZ diagnosis were separately generated based on gut microbial and neuroimaging data.
Gut microbial dysbiosis, characterized by a decrease in butyrate-producing bacteria and an increase in proinflammatory bacteria, has been identified in SZ patients. These key microbial taxa were associated with increased inflammatory cytokines, potentially through mediating lipid metabolic pathways such as steroid biosynthesis and linoleic acid metabolism. Further analysis revealed altered microbial genera to be correlated with disrupted gray matter volume and regional homogeneity in SZ patients. Importantly, certain inflammatory cytokines mediated the relationship between the SZ-enriched genus and aberrant activity of anterior cingulate cortex and left inferior temporal gyrus in the SZ group. Moreover, the classification model based on gut microbial data showed comparable efficacy to the model based on brain functional signatures in SZ diagnosis.
This study presents evidence for the dysregulated microbiota-gut-brain axis in SZ and emphasizes the central role of peripheral inflammation.
肠道微生物群与精神分裂症（SZ）的发病机制及大脑的相关变化有关，但其潜在机制仍不清楚。本研究旨在探讨以SZ患者外周炎症为中心的微生物-肠道-脑轴相互作用。
我们招募了182例SZ患者和120名健康对照（HC）。收集并综合分析了多组学数据，包括粪便16S rRNA、细胞因子数据和神经影像学数据。利用多组学相关性和中介分析来确定肠道微生物群与炎性细胞因子及神经影像学特征之间的关联。此外，分别基于肠道微生物和神经影像学数据生成了用于SZ有效诊断的机器学习模型。
在SZ患者中发现了肠道微生物失调，其特征是产丁酸菌减少和促炎菌增加。这些关键的微生物分类群与炎性细胞因子增加有关，可能是通过介导脂质代谢途径，如类固醇生物合成和亚油酸代谢。进一步分析发现，SZ患者中微生物属的改变与灰质体积和区域同质性的破坏有关。重要的是，某些炎性细胞因子介导了SZ组中富含SZ的属与前扣带回皮质和左颞下回异常活动之间的关系。此外，基于肠道微生物数据的分类模型在SZ诊断中显示出与基于脑功能特征的模型相当的效能。
本研究为SZ中失调的微生物-肠道-脑轴提供了证据，并强调了外周炎症的核心作用。
