Department of Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, 710061, China; Center for Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, 710061, China; Clinical Research Center for Psychiatric Medicine of Shaanxi Province, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, 710061, China.
Department of Psychiatry, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, 710061, China; Center for Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, 710061, China; Clinical Research Center for Psychiatric Medicine of Shaanxi Province, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, 710061, China; Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.
J Psychiatr Res. 2022 Sep;153:125-133. doi: 10.1016/j.jpsychires.2022.07.006. Epub 2022 Jul 5.
Amino acid abnormalities have been suggested to be a key pathophysiological mechanism in schizophrenia (SZ). Recently, gut microbes were found to be critically involved in mental and metabolic diseases. However, the relationship between serum amino acid levels and gut microbes in SZ is rarely studied. Here, we analyzed serum amino acid levels in 76 untreated SZ patients and 79 healthy controls (HC). Serum levels of 10 amino acids were significantly altered in patients with SZ. We further classified the cut-off values for serum arginine, leucine, glutamine, and methionine levels to distinguish SZ patients from controls. These classifiers were shown to be effective in another validation cohort (49 SZ and 48 HC). The correlation between serum amino acids and clinical symptoms and cognitive functions was also analyzed. Arginine, leucine, glutamine, and methionine levels were significantly correlated with clinical symptoms and cognitive impairments in SZ patients. By metagenome shotgun sequencing of fecal samples, we found that patients with SZ with a low level of serum amino acids have higher richness and evenness of the gut microbiota. At the genus level, the abundances of Mitsuokella and Oscillibacter are significantly abnormal. At the mOTU level, 15 mOTUs in the low-level SZ group were significantly different from the HC group. In addition, Mitsuokella multacida was correlated with glutamine and methionine, respectively. Our research revealed that alterations in serum amino acid levels are critically related to changes in gut microbiota composition in SZ patients. These findings may shed light on new strategies for the diagnosis and treatment of SZ.
氨基酸异常被认为是精神分裂症（SZ）的关键病理生理机制。最近，肠道微生物被发现与精神和代谢疾病密切相关。然而，SZ 患者血清氨基酸水平与肠道微生物之间的关系很少被研究。在这里，我们分析了 76 名未经治疗的 SZ 患者和 79 名健康对照者（HC）的血清氨基酸水平。SZ 患者的血清中有 10 种氨基酸水平显著改变。我们进一步将血清精氨酸、亮氨酸、谷氨酰胺和蛋氨酸水平的截断值分类，以区分 SZ 患者和对照者。这些分类器在另一个验证队列（49 名 SZ 和 48 名 HC）中显示有效。还分析了血清氨基酸与临床症状和认知功能之间的相关性。精氨酸、亮氨酸、谷氨酰胺和蛋氨酸水平与 SZ 患者的临床症状和认知障碍显著相关。通过粪便样本的宏基因组鸟枪法测序，我们发现血清氨基酸水平低的 SZ 患者的肠道微生物群落丰富度和均匀度更高。在属水平上，Mitsuokella 和 Oscillibacter 的丰度明显异常。在 mOTU 水平上，低水平 SZ 组的 15 个 mOTU 与 HC 组有显著差异。此外，Mitsuokella multacida 分别与谷氨酰胺和蛋氨酸相关。我们的研究表明，血清氨基酸水平的改变与 SZ 患者肠道微生物群落组成的变化密切相关。这些发现可能为 SZ 的诊断和治疗提供新策略。
