Yuan Xiuxia, Li Xue, Hei Gangrui, Zhang Xiaoyun, Song Xueqin
Department of Psychiatry, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Henan International Joint Laboratory of Biological Psychiatry, Zhengzhou, China; Henan Psychiatric Transformation Research Key Laboratory, Zhengzhou University, Zhengzhou, China.
Department of Psychiatry, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Henan International Joint Laboratory of Biological Psychiatry, Zhengzhou, China; Henan Psychiatric Transformation Research Key Laboratory, Zhengzhou University, Zhengzhou, China.
Behav Brain Res. 2024 Aug 24;472:115149. doi: 10.1016/j.bbr.2024.115149. Epub 2024 Jul 14.
The microbiome-gut-brain axis is related to schizophrenia (SCZ). The role of intestinal mycobiota in SCZ has been under investigated. We present a half-year follow-up study involving 109 chronic SCZ patients and 77 healthy controls. Intestinal mycobiota was tested by internal transcribed spacer (ITS). Untargeted liquid chromatography-mass spectrometry (LC-MS) was used to measure fecal metabolites. Symptom severity was assessed using the Positive and Negative Syndrome Scale. Enterotype analysis showed that Candida-type patients exhibited severer positive symptoms and depression factors than Saccharomyces-type patients. Candida and its top species and operational taxonomic units (OTUs) were positively correlated with depression factors (all p=0.001). Fecal metabolites analysis showed that upregulated metabolites were associated with chronic inflammation (NF-κB pathway and T helper cell differentiation), downregulated metabolites were associated with glutamate metabolism, serotonergic and dopaminergic synapse. Procrustes analysis revealed significant correlation between intestinal mycobiota and fecal metabolites (M2=0.937, p<0.001). Metabolic module analysis showed that the top module, MEturquoise (associated with Th1 and Th2 cell differentiation), was negatively correlated with SCZ (r=-0.783, p<0.0001), positively correlated with Candida, Aspergillus, Trichosporon and Talaromyces (decreased in SCZ) and negatively correlated with Saccharomyces (increased in SCZ). We also found impairments of intestinal barrier in SCZ, characterized by increased in blood D-lactate (mucosa impairment marker) and decreased in blood mucin 2 (mucosal barrier protective protein). Serum levels of TNF-α was increased and showed stable high levels during treatment. This study suggests that mycobiota dysbiosis-related chronic inflammation and an impaired intestinal mucosal barrier are associated with chronic SCZ.
微生物群-肠-脑轴与精神分裂症（SCZ）相关。肠道真菌群在精神分裂症中的作用一直未得到充分研究。我们开展了一项为期半年的随访研究，纳入了109例慢性精神分裂症患者和77名健康对照。通过内转录间隔区（ITS）检测肠道真菌群。采用非靶向液相色谱-质谱联用（LC-MS）测定粪便代谢产物。使用阳性和阴性症状量表评估症状严重程度。肠型分析显示，念珠菌型患者比酿酒酵母型患者表现出更严重的阳性症状和抑郁因子。念珠菌及其优势菌种和可操作分类单元（OTUs）与抑郁因子呈正相关（所有p = 0.001）。粪便代谢产物分析表明，上调的代谢产物与慢性炎症（NF-κB通路和辅助性T细胞分化）相关，下调的代谢产物与谷氨酸代谢、血清素能和多巴胺能突触相关。Procrustes分析显示肠道真菌群与粪便代谢产物之间存在显著相关性（M2 = 0.937，p < 0.001）。代谢模块分析表明，顶级模块MEturquoise（与Th1和Th2细胞分化相关）与精神分裂症呈负相关（r = -0.783，p < 0.0001），与念珠菌、曲霉、毛孢子菌和拟青霉呈正相关（在精神分裂症中减少），与酿酒酵母呈负相关（在精神分裂症中增加）。我们还发现精神分裂症患者存在肠道屏障损伤，表现为血液中D-乳酸（黏膜损伤标志物）升高和血液中粘蛋白2（黏膜屏障保护蛋白）降低。血清TNF-α水平升高，且在治疗期间保持稳定的高水平。这项研究表明，真菌群失调相关的慢性炎症和肠道黏膜屏障受损与慢性精神分裂症有关。
