Emerging evidence has linked the gut microbiome changes to schizophrenia. However, there has been limited research into the functional pathways by which the gut microbiota contributes to the phenotype of persons with chronic schizophrenia. We characterized the composition and functional potential of the gut microbiota in 48 individuals with chronic schizophrenia and 48 matched (sequencing plate, age, sex, BMI, and antibiotic use) non-psychiatric comparison subjects (NCs) using 16S rRNA sequencing. Patients with schizophrenia demonstrated significant beta-diversity differences in microbial composition and predicted genetic functional potential compared to NCs. Alpha-diversity of taxa and functional pathways were not different between groups. Random forests analyses revealed that the microbiome predicts differentiation of patients with schizophrenia from NCs using taxa (75% accuracy) and functional profiles (67% accuracy for KEGG orthologs, 70% for MetaCyc pathways). We utilized a new compositionally-aware method incorporating reference frames to identify differentially abundant microbes and pathways, which revealed that Lachnospiraceae is associated with schizophrenia. Functional pathways related to trimethylamine-N-oxide reductase and Kdo2-lipid A biosynthesis were altered in schizophrenia. These metabolic pathways were associated with inflammatory cytokines and risk for coronary heart disease in schizophrenia. Findings suggest potential mechanisms by which the microbiota may impact the pathophysiology of the disease through modulation of functional pathways related to immune signaling/response and lipid and glucose regulation to be further investigated in future studies.

中文翻译：

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精神分裂症的肠道微生物组：与免疫调节和动脉粥样硬化风险相关的功能途径改变


新的证据表明肠道微生物组的变化与精神分裂症有关。然而，对于肠道微生物群影响慢性精神分裂症患者表型的功能途径的研究还很有限。我们使用 16S rRNA 测序对 48 名慢性精神分裂症患者和 48 名匹配（测序板、年龄、性别、BMI 和抗生素使用）非精神病对照受试者 (NC) 的肠道微生物群的组成和功能潜力进行了表征。与NC患者相比，精神分裂症患者在微生物组成和预测的遗传功能潜力方面表现出显着的β多样性差异。类群和功能途径的α多样性在各组之间没有差异。随机森林分析显示，微生物组使用分类群（准确度为 75%）和功能概况（KEGG 直向同源物的准确度为 67%，MetaCyc 通路的准确度为 70%）来预测精神分裂症患者与 NC 患者的分化。我们利用一种新的成分感知方法，结合参考系来识别差异丰度的微生物和途径，结果表明毛螺菌科与精神分裂症有关。精神分裂症中与三甲胺-N-氧化物还原酶和 Kdo2-脂质 A 生物合成相关的功能途径发生了改变。这些代谢途径与精神分裂症患者的炎症细胞因子和冠心病风险相关。研究结果表明，微生物群可能通过调节与免疫信号/反应以及脂质和葡萄糖调节相关的功能途径来影响疾病的病理生理学，这些机制有待在未来的研究中进一步研究。