精神分裂症肠道微生物与脑影像和临床表征的关系

doi:10.3724/SP.J.1042.2022.01856

摘要/Abstract

摘要：

微生物-肠-脑轴假设在精神分裂症发病机制中的研究受到越来越多的关注。以往研究初步考察了肠道微生物的构成与精神分裂症患者脑影像和临床表征之间的联系, 但具体的作用路径尚不明确。当前研究通过总结最新研究进展, 并在此基础上提出肠道微生物影响精神分裂症患者大脑结构和功能的机制假设。相关内容对于进一步阐明精神分裂症的病理机制, 为将肠道微生物纳入精神分裂症的评估与干预提供理论基础。

关键词: 精神分裂症, 肠道微生物, 微生物-肠-脑轴, 脑影像, 临床表征

Abstract:

The microbiota-gut-brain axis hypothesis has attracted more and more attention in the research of the pathogenesis of schizophrenia. This hypothesis stated that gut microbiota can cause inflammation in the brain of patients with schizophrenia and cause abnormalities of brain function through the intestinal immune system, and that early colonization of gut microbiota will affect the development of the central nervous system in patients with schizophrenia and thus cause abnormalities of brain structure. Previous research has preliminarily investigated the relationship between the composition of gut microbiota and the brain imaging and clinical manifestation of patients with schizophrenia, but the specific action path is still unclear.

In the current research, we have summarized the latest research progress and found that the gut microbiota diversity of patients with schizophrenia is significantly lower than that of the normal control, and the relative abundance of gut microbiota is also significantly different from that of the normal control at different biological levels, which is mainly manifested as the increase in the relative abundance of Actinomycetes and Proteus as well as the decrease in the relative abundance of Bacteroides and Sclerotinia. Based on the brain imaging results of patients with schizophrenia, we found that there was a significant correlation between the diversity of gut microbiota and the relative abundance of certain microbiota and the gray volume of specific areas of the patient's brain, including the right middle frontal gyrus, the right postcentral gyrus and insula, as well as the Amplitude of Low Frequency Fluctuation index (ALFF) and Regional Homogeneity index (ReHo) in certain brain functional areas, which were mainly reflected in the functional signals of the frontal and temporal lobes. Further combined with the clinical manifestation analysis of patients with schizophrenia, the results showed that there was a significant correlation between the composition of gut microbiota and the cognitive function scores as well as the clinical symptom score (PANSS). The α diversity of gut microbiota was related to visual hallucination, and the relative abundance of Sclerotinia sclerotiorum was significantly and positively correlated with the negative symptom score.

These evidences indicate that the potential role of gut microbiota in schizophrenia is related to the changes of brain structure and function. Based on the ability of gut microbiota to identify and produce chemicals and the evidence of severe neurotransmitter imbalance in patients with schizophrenia, we proposed the mechanism hypothesis of gut microbiota affecting the brain structure and function of patients with schizophrenia, believing that gut microbiota may affect the brain structure and function of patients with schizophrenia through immune mediated pathway, short-chain fatty acid pathway, kynurenine pathway and brain-derived neurotrophic factor pathway. The related contents will provide new insights for further elucidation of the pathological mechanism of schizophrenia, clarify how gut microbiota affect the potential pathophysiological process of schizophrenia through the microbiota-gut-brain axis, and provide a theoretical basis for the inclusion of gut microbiota in the diagnosis, evaluation and intervention of schizophrenia.

Key words: schizophrenia, gut microbiota, microbiota-gut-brain axis, brain imaging, clinical manifestation

中图分类号:

B845

周振友, 孔丽, 陈楚侨. (2022). 精神分裂症肠道微生物与脑影像和临床表征的关系. 心理科学进展 , 30(8), 1856-1869.

ZHOU Zhenyou, KONG Li, CHAN Raymond. (2022). The relationship between gut microbiota and brain imaging and clinical manifestation in schizophrenia. Advances in Psychological Science, 30(8), 1856-1869.

图/表 3

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研究者	SCZ组/HC组	相对丰度	多样性
Shen et al., 2018	64/53	增加：门水平：变形菌属水平：琥珀酰菌、巨球孢菌、柯林塞拉菌、梭状芽孢杆菌、克雷伯氏菌和甲烷菌减少：属水平：布拉氏菌、粪球菌、玫瑰菌
Schwarz et al., 2018	28/16	增加：科水平：乳杆菌科、Halothiobacillaceae、布鲁氏菌科和微球菌科属水平：乳杆菌属、Tropheryma、Halothiobacillus、Saccharophagus、Ochrobactrum, Deferribacter和Halorubrum 减少：科水平：韦氏球菌科属水平：Anabaena、Nitrosospira和Gallionella
Nguyen et al., 2019	25/25	增加：属水平：厌氧球菌属减少：门水平：变形菌门属水平：流感嗜血杆菌属、萨特氏菌属和梭菌属	精神分裂症组与健康对照组的肠道菌群α多样性之间无显著差异。
Xu et al., 2020	84/84	增加：门水平：放线菌门目水平：放线菌目和鞘氨醇目科水平：鞘氨醇科属水平：埃格氏菌属和巨球孢菌属, 粘杆菌属, 青春双歧杆菌, 产气荚膜梭菌减少：目水平：红串珠目科水平：产碱杆菌科, 肠球菌科, 明串珠科, 红串珠科属水平：肠球菌属	精神分裂症患者组肠道菌群多样性显著低于对照组
Li et al., 2020	82/80	增加：门水平：放线菌属水平：柯林塞拉氏菌、乳杆菌、琥珀杆菌、莫格巴杆菌、棒状杆菌、未定义乳球菌和未定义真细菌减少：门水平：厚壁菌门属水平：Adlercreutzia、Anaerostipes、乳球菌和粪链球菌	α多样性在两组之间没有显著差异, 但是β多样性表明两组之间的微生物组组成存在显着的群落水平分离
Manchia et al., 2021	38/20	缺失：门水平：蓝细菌门科水平：巴氏杆菌科, cytophagaceae和morganellaceae, 属水平：醋酸杆菌属、嗜血杆菌属、Turicibacter, Obesumbacterium等种水平：马链球菌种、粪球菌种、血链球菌种等	精神分裂症组的α多样性的Shannon指数显著低于健康对照组。
赵星梅 et al., 2019	16/18	增加：门水平：放线菌门属水平：双歧杆菌属、普雷沃菌属和巨单胞菌属减少：门水平：拟杆菌门和软壁菌门属水平：拟杆菌属和柔嫩梭菌属	α多样性的Ace指数、Chao指数、Shannon指数患者组显著低于健康组, Simpson指数明显高于健康对照组

研究者	SCZ组/HC组	相对丰度	多样性
Shen et al., 2018	64/53	增加：门水平：变形菌属水平：琥珀酰菌、巨球孢菌、柯林塞拉菌、梭状芽孢杆菌、克雷伯氏菌和甲烷菌减少：属水平：布拉氏菌、粪球菌、玫瑰菌
Schwarz et al., 2018	28/16	增加：科水平：乳杆菌科、Halothiobacillaceae、布鲁氏菌科和微球菌科属水平：乳杆菌属、Tropheryma、Halothiobacillus、Saccharophagus、Ochrobactrum, Deferribacter和Halorubrum 减少：科水平：韦氏球菌科属水平：Anabaena、Nitrosospira和Gallionella
Nguyen et al., 2019	25/25	增加：属水平：厌氧球菌属减少：门水平：变形菌门属水平：流感嗜血杆菌属、萨特氏菌属和梭菌属	精神分裂症组与健康对照组的肠道菌群α多样性之间无显著差异。
Xu et al., 2020	84/84	增加：门水平：放线菌门目水平：放线菌目和鞘氨醇目科水平：鞘氨醇科属水平：埃格氏菌属和巨球孢菌属, 粘杆菌属, 青春双歧杆菌, 产气荚膜梭菌减少：目水平：红串珠目科水平：产碱杆菌科, 肠球菌科, 明串珠科, 红串珠科属水平：肠球菌属	精神分裂症患者组肠道菌群多样性显著低于对照组
Li et al., 2020	82/80	增加：门水平：放线菌属水平：柯林塞拉氏菌、乳杆菌、琥珀杆菌、莫格巴杆菌、棒状杆菌、未定义乳球菌和未定义真细菌减少：门水平：厚壁菌门属水平：Adlercreutzia、Anaerostipes、乳球菌和粪链球菌	α多样性在两组之间没有显著差异, 但是β多样性表明两组之间的微生物组组成存在显着的群落水平分离
Manchia et al., 2021	38/20	缺失：门水平：蓝细菌门科水平：巴氏杆菌科, cytophagaceae和morganellaceae, 属水平：醋酸杆菌属、嗜血杆菌属、Turicibacter, Obesumbacterium等种水平：马链球菌种、粪球菌种、血链球菌种等	精神分裂症组的α多样性的Shannon指数显著低于健康对照组。
赵星梅 et al., 2019	16/18	增加：门水平：放线菌门属水平：双歧杆菌属、普雷沃菌属和巨单胞菌属减少：门水平：拟杆菌门和软壁菌门属水平：拟杆菌属和柔嫩梭菌属	α多样性的Ace指数、Chao指数、Shannon指数患者组显著低于健康组, Simpson指数明显高于健康对照组

研究对象	干预方式	测量方法	结果				参考
研究对象	干预方式	测量方法	神经影像结果	GM结果	相关关系	其他	参考
住院精神分裂症患者(SCZ)、健康对照组(HCs)	无干预(住院精神分裂症患者21人, 健康对照组30人)	功能磁共振扫描SIEMENS3.0T Primage (粪便样本), PANSS评估	SCZ的ALFF指数的在双侧枕叶、后顶叶显著下降, 双内侧前额叶、外侧前额叶、内侧颞叶显著上升, 颞上回、双侧枕叶的ReHo值显著下降, 内侧前额叶及外侧前额叶的ReHo值显著上升。	与HCs组相比, SCZ组的的放线菌门及其下属的红蝽菌纲等菌群丰度上升, 变形菌门下属的海洋螺菌目等丰度显著上升。	基于ALFF与菌群的相关性分析发现：放线菌门与外侧前额叶、右侧额中回显著正相关; Acidminococcaccac的相对丰度与枕叶的ALFF值成显著正相关, 而与颞叶呈负相关。	SCZ患者肠道菌群中红蝽菌纲相对丰度升高可能是精神分裂症的一个诱因(阴性症状、认知受损)	吴位东, 2019
首发精神分裂症(FSCZ)、长期用药精神分裂症(TSCZ)、健康对照(HCs)	无干预(首发40人、长期用药85人、健康对照69人)	磁共振结构成像、GM (粪便样本)	SCZ患者与HCs之间总灰质体积无显著差异, SCZ患者的右侧额中回的灰质体积显著增加。	科水平上：与HCs组相比, FSCZ患者克里斯滕森科、肠杆菌科和骆驼蓬科丰度上升, 巴斯德氏菌科、旅游杆菌科、消化链球菌科、韦氏菌科、琥珀酰菌科的丰度下降。	偏相关分析发现放线杆菌属和韦氏菌科的相对丰度与FSCZ患者的右侧额中回的灰质体积呈正相关	FSCZ和TSCZ患者的肠道生物的改变是SCZ固有的特征, 与抗精神病药物治疗没有特别的相关性。	Ma et al., 2020
精神分裂症患者(SCZ), 健康对照组(HCs)	无干预(SCZ患者38人, HCs38人)	磁共振结构成像、GM (粪便样本)	SCZ患者和HCs在16个脑区的灰质体积存在显著差异, SCZ患者和HCs患者在34个脑区的ReHo值存在显著差异, 只有一个脑区表现出显著的组间ALFF差异。与NCs相比, SZ患者某些脑区的灰质体积降低, 包括双侧岛叶、额叶和颞叶区域。	两组之间在α多样性的任何水平上都没有显著差异。与HC组比较, SCZ组乳球菌和玫瑰球菌的相对丰度显著下降, SCZ组的Veillonella相对丰度显著上升,	SCZ患者肠道菌群的α多样性均匀度和Shannon指数与大脑某些区域的灰质体积和ReHo值呈正相关; SCZ患者中的右侧颞上回、左侧楔叶和右侧颞中回的ReHo值与蔷薇属的相对丰度呈负相关。		Li et al., 2021

研究对象	干预方式	测量方法	结果				参考
研究对象	干预方式	测量方法	神经影像结果	GM结果	相关关系	其他	参考
住院精神分裂症患者(SCZ)、健康对照组(HCs)	无干预(住院精神分裂症患者21人, 健康对照组30人)	功能磁共振扫描SIEMENS3.0T Primage (粪便样本), PANSS评估	SCZ的ALFF指数的在双侧枕叶、后顶叶显著下降, 双内侧前额叶、外侧前额叶、内侧颞叶显著上升, 颞上回、双侧枕叶的ReHo值显著下降, 内侧前额叶及外侧前额叶的ReHo值显著上升。	与HCs组相比, SCZ组的的放线菌门及其下属的红蝽菌纲等菌群丰度上升, 变形菌门下属的海洋螺菌目等丰度显著上升。	基于ALFF与菌群的相关性分析发现：放线菌门与外侧前额叶、右侧额中回显著正相关; Acidminococcaccac的相对丰度与枕叶的ALFF值成显著正相关, 而与颞叶呈负相关。	SCZ患者肠道菌群中红蝽菌纲相对丰度升高可能是精神分裂症的一个诱因(阴性症状、认知受损)	吴位东, 2019
首发精神分裂症(FSCZ)、长期用药精神分裂症(TSCZ)、健康对照(HCs)	无干预(首发40人、长期用药85人、健康对照69人)	磁共振结构成像、GM (粪便样本)	SCZ患者与HCs之间总灰质体积无显著差异, SCZ患者的右侧额中回的灰质体积显著增加。	科水平上：与HCs组相比, FSCZ患者克里斯滕森科、肠杆菌科和骆驼蓬科丰度上升, 巴斯德氏菌科、旅游杆菌科、消化链球菌科、韦氏菌科、琥珀酰菌科的丰度下降。	偏相关分析发现放线杆菌属和韦氏菌科的相对丰度与FSCZ患者的右侧额中回的灰质体积呈正相关	FSCZ和TSCZ患者的肠道生物的改变是SCZ固有的特征, 与抗精神病药物治疗没有特别的相关性。	Ma et al., 2020
精神分裂症患者(SCZ), 健康对照组(HCs)	无干预(SCZ患者38人, HCs38人)	磁共振结构成像、GM (粪便样本)	SCZ患者和HCs在16个脑区的灰质体积存在显著差异, SCZ患者和HCs患者在34个脑区的ReHo值存在显著差异, 只有一个脑区表现出显著的组间ALFF差异。与NCs相比, SZ患者某些脑区的灰质体积降低, 包括双侧岛叶、额叶和颞叶区域。	两组之间在α多样性的任何水平上都没有显著差异。与HC组比较, SCZ组乳球菌和玫瑰球菌的相对丰度显著下降, SCZ组的Veillonella相对丰度显著上升,	SCZ患者肠道菌群的α多样性均匀度和Shannon指数与大脑某些区域的灰质体积和ReHo值呈正相关; SCZ患者中的右侧颞上回、左侧楔叶和右侧颞中回的ReHo值与蔷薇属的相对丰度呈负相关。		Li et al., 2021