不同时期精神分裂症患者血浆脂多糖水平与肠道菌群特征的比较及相关性研究

Comparison and Correlation Study of Plasma Lipopolysaccharide Levels and Gut Microbiota Characteristics in Patients with Schizophrenia at Different Stages

摘要: 目的：比较不同时期精神分裂症患者的血浆脂多糖水平和肠道菌群特征的变化及其相关性，探索肠道菌群的改变在精神分裂症患者疾病进展中的潜在机制。方法：纳入不同时期的精神分裂症患者(急性期19例、缓解期22例)，收集受试者的一般资料，采集受试者血浆和粪便样本，检测其血浆中的脂多糖水平，采用16S rRNA基因高通量测序分析其肠道菌群特征，并探究精神分裂症患者的肠道菌群与血浆脂多糖水平的相关性。结果：不同时期精神分裂症患者的血浆脂多糖水平均高于健康对照组(P < 0.05)，但急性组与缓解组间血浆LPS水平无显著差异(P = 0.263)。精神分裂症患者急性组的肠道菌群Alpha多样性Chao1、Ace、Shannon指数高于缓解组(P < 0.05)，不同时期精神分裂症患者的肠道菌群Beta多样性差异不存在统计学意义(P > 0.05)；精神分裂症急性组和缓解组肠道菌群物种组成不同；与缓解组相比，精神分裂症急性组的拟杆菌门(p_Bacteroidota)、拟杆菌纲(c_Bacteroidia)、拟杆菌目(o_Bacteroidales)相对丰度较高(P < 0.05)。急性组血浆脂多糖水平与拟杆菌门(p_Bacteroidota)、拟杆菌纲(c_Bacteroidia)、拟杆菌目(o_Bacteroidales)、酸杆菌门(Acidobacteriota)、冷杆菌属(Psychrobacter)呈正相关(P < 0.05)；缓解组血浆脂多糖水平与拟杆菌门(p_Bacteroidota)、拟杆菌纲(c_Bacteroidia)呈正相关(P < 0.05)。结论：血浆脂多糖水平升高及肠道菌群多样性、组成的改变是精神分裂症患者的重要生物学特征，且不同疾病时期的肠道菌群与血浆脂多糖的关联存在差异，这为进一步探索肠道菌群通过调控LPS相关炎症通路参与SCZ疾病进展的机制提供了实验依据。

Abstract: Objective: To compare the changes in plasma lipopolysaccharide (LPS) levels and gut microbiota characteristics as well as their correlations among patients with schizophrenia at different stages, and to explore the potential mechanism of gut microbiota alterations in the progression of schizophrenia. Methods: Patients with schizophrenia at different stages (19 in the acute phase and 22 in the remission phase) were enrolled. General information of the subjects was collected, and their plasma and fecal samples were obtained. Plasma LPS levels were detected, and 16S rRNA gene high-throughput sequencing was used to analyze the characteristics of gut microbiota. Additionally, the correlation between gut microbiota and plasma LPS levels in patients with schizophrenia was explored. Results: Plasma LPS levels in patients with schizophrenia at different stages were significantly higher than those in the healthy control group (P < 0.05), but there was no significant difference in plasma LPS levels between the acute phase group and the remission phase group (P = 0.263). The Alpha diversity indices (Chao1, Ace, and Shannon) of gut microbiota in the acute phase group were higher than those in the remission phase group (P < 0.05), there was no statistically significant difference in gut microbiota Beta diversity among patients with schizophrenia at different phases (P > 0.05); there were differences in the species composition of gut microbiota between the acute phase group and the remission phase group; compared with the remission phase group, the acute phase group had a higher relative abundance of p_Bacteroidota, c_Bacteroidia, and o_Bacteroidales (P < 0.05). In the acute phase group, plasma LPS levels were positively correlated with p_Bacteroidota, c_Bacteroidia, o_Bacteroidales, Acidobacteriota, and Psychrobacter (P < 0.05); in the remission phase group, plasma LPS levels were positively correlated with p_Bacteroidota and c_Bacteroidia (P < 0.05). Conclusion: Elevated plasma LPS levels and changes in gut microbiota diversity and composition are important biological characteristics of patients with schizophrenia, and there are differences in the association between gut microbiota and plasma LPS at different disease stages. This provides experimental evidence for further exploring the mechanism by which gut microbiota is involved in the progression of SCZ through regulating LPS-related inflammatory pathways.