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肠道促炎细菌与未用药的重度抑郁症患者海马体功能连接异常有关。

Gut proinflammatory bacteria is associated with abnormal functional connectivity of hippocampus in unmedicated patients with major depressive disorder.

机构信息

Medical Imaging Center, First Affiliated Hospital of Jinan University, Guangzhou, China.

Institute of Molecular and Functional Imaging, Jinan University, Guangzhou, China.

出版信息

Transl Psychiatry. 2024 Jul 16;14(1):292. doi: 10.1038/s41398-024-03012-9.

DOI:10.1038/s41398-024-03012-9
PMID:39013880
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11253007/
Abstract

Accumulating evidence has revealed the gut bacteria dysbiosis and brain hippocampal functional and structural alterations in major depressive disorder (MDD). However, the potential relationship between the gut microbiota and hippocampal function alterations in patients with MDD is still very limited. Data of resting-state functional magnetic resonance imaging were acquired from 44 unmedicated MDD patients and 42 demographically matched healthy controls (HCs). Severn pairs of hippocampus subregions (the bilateral cornu ammonis [CA1-CA3], dentate gyrus (DG), entorhinal cortex, hippocampal-amygdaloid transition area, and subiculum) were selected as the seeds in the functional connectivity (FC) analysis. Additionally, fecal samples of participants were collected and 16S rDNA amplicon sequencing was used to identify the altered relative abundance of gut microbiota. Then, association analysis was conducted to investigate the potential relationships between the abnormal hippocampal subregions FC and microbiome features. Also, the altered hippocampal subregion FC values and gut microbiota levels were used as features separately or together in the support vector machine models distinguishing the MDD patients and HCs. Compared with HCs, patients with MDD exhibited increased FC between the left hippocampus (CA2, CA3 and DG) and right hippocampus (CA2 and CA3), and decreased FC between the right hippocampal CA3 and bilateral posterior cingulate cortex. In addition, we found that the level of proinflammatory bacteria (i.e., Enterobacteriaceae) was significantly increased, whereas the level of short-chain fatty acids producing-bacteria (i.e., Prevotellaceae, Agathobacter and Clostridium) were significantly decreased in MDD patients. Furthermore, FC values of the left hippocampal CA3- right hippocampus (CA2 and CA3) was positively correlated with the relative abundance of Enterobacteriaceae in patients with MDD. Moreover, altered hippocampal FC patterns and gut microbiota level were considered in combination, the best discrimination was obtained (AUC = 0.92). These findings may provide insights into the potential role of gut microbiota in the underlying neuropathology of MDD patients.

摘要

越来越多的证据表明,在重度抑郁症(MDD)患者中,肠道细菌失调和大脑海马体功能及结构改变。然而,MDD 患者肠道微生物群与海马体功能改变之间的潜在关系仍然非常有限。对 44 名未接受药物治疗的 MDD 患者和 42 名年龄匹配的健康对照者(HCs)的静息状态功能磁共振成像数据进行了采集。在功能连接(FC)分析中选择了 7 对海马亚区(双侧角回[CA1-CA3]、齿状回[DG]、内嗅皮质、海马杏仁核过渡区和下托)作为种子。此外,收集了参与者的粪便样本,并进行了 16S rDNA 扩增子测序,以确定肠道微生物群特征的相对丰度改变。然后,进行关联分析以调查异常海马亚区 FC 与微生物组特征之间的潜在关系。此外,将改变的海马亚区 FC 值和肠道微生物群水平分别或一起作为特征用于支持向量机模型中,以区分 MDD 患者和 HCs。与 HCs 相比,MDD 患者左侧海马(CA2、CA3 和 DG)和右侧海马(CA2 和 CA3)之间的 FC 增加,右侧海马 CA3 与双侧后扣带回之间的 FC 减少。此外,我们发现促炎细菌(即肠杆菌科)的水平显著增加,而短链脂肪酸产生菌(即普雷沃氏菌科、Agathobacter 和梭菌)的水平在 MDD 患者中显著降低。此外,MDD 患者左侧海马 CA3-右侧海马(CA2 和 CA3)的 FC 值与肠杆菌科的相对丰度呈正相关。此外,将改变的海马 FC 模式和肠道微生物群水平结合起来考虑,可以获得最佳的区分效果(AUC=0.92)。这些发现可能为肠道微生物群在 MDD 患者潜在神经病理学中的作用提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70b5/11253007/46dc6e762099/41398_2024_3012_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70b5/11253007/83ce2019dd78/41398_2024_3012_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70b5/11253007/7612eb2ec76d/41398_2024_3012_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70b5/11253007/46dc6e762099/41398_2024_3012_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70b5/11253007/83ce2019dd78/41398_2024_3012_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70b5/11253007/59511e790c0c/41398_2024_3012_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70b5/11253007/7612eb2ec76d/41398_2024_3012_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70b5/11253007/46dc6e762099/41398_2024_3012_Fig4_HTML.jpg

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