From the Institute of Brain Science (Wang, Liu, Wu, Lu), Faculty of Medicine (Tsai, Wang, Lu), Institute of Philosophy of Mind and Cognition (Tu), Department of Biomedical Engineering (Chang), the National Yang Ming Chiao Tung University, Taipei, Taiwan; the Endoscopy Center for Diagnosis and Treatment (Wang, Liu, Lu), Department of Medicine (Wang, Lu), Division of Gastroenterology, Department of Psychiatry (Tu, Chang), Department of Medical Research (Tu, Chang), Department of Dietetics & Nutrition (Wu), Taipei Veterans General Hospital, Taipei, Taiwan; the Institute of Information Science (Chuang, Lin), Academia Sinica, Taiwan; Yours Clinic (Tsai), Taipei, Taiwan.
From the Institute of Brain Science (Wang, Liu, Wu, Lu), Faculty of Medicine (Tsai, Wang, Lu), Institute of Philosophy of Mind and Cognition (Tu), Department of Biomedical Engineering (Chang), the National Yang Ming Chiao Tung University, Taipei, Taiwan; the Endoscopy Center for Diagnosis and Treatment (Wang, Liu, Lu), Department of Medicine (Wang, Lu), Division of Gastroenterology, Department of Psychiatry (Tu, Chang), Department of Medical Research (Tu, Chang), Department of Dietetics & Nutrition (Wu), Taipei Veterans General Hospital, Taipei, Taiwan; the Institute of Information Science (Chuang, Lin), Academia Sinica, Taiwan; Yours Clinic (Tsai), Taipei, Taiwan
J Psychiatry Neurosci. 2024 Sep 19;49(5):E289-E300. doi: 10.1503/jpn.240050. Print 2024 Sep-Oct.
BACKGROUND: Increasing evidence suggests an important role of the gut microbiome in the pathogenesis of mental disorders, including depression, along the microbiota-gut-brain axis. We sought to explore the interactions between gut microbe composition and neural circuits in late-life depression (LLD). METHODS: We performed fecal 16S ribosomal RNA (rRNA) sequencing and resting-state functional magnetic resonance imaging in a case-control cohort of older adults with LLD and healthy controls to characterize the association between gut microbiota and brain functional connectivity (FC). We used the Hamilton Depression Rating Scale (HAMD) to assess depressive symptoms. RESULTS: We included 32 adults with LLD and 16 healthy controls. At the genus level, the relative abundance of , , , , and was significantly higher among patients with LDD than controls. Reduced FC within mood regulation circuits was mainly found in the frontal cortex (e.g., the right superior and inferior frontal gyrus, right lateral occipital cortex, left middle frontal gyrus, and left caudate) among patients with MDD. Group-characterized gut microbes among controls and patients showed opposite correlations with seed-based FC, which may account for the aberrant emotion regulation among patients with LDD. The abundance of (dominant genus among patients with LLD) was positively correlated with both HAMD scores ( = 0.49, = 0.0004) and group-characterized FC ( = -0.37, < 0.05), while (dominant genus among controls) was negatively correlated with both HAMD scores ( = -0.30, = 0.04) and group-characterized FC. LIMITATIONS: The study's cross-sectional design and small sample size limit causal inferences; larger longitudinal studies are required for detailed subgroup analyses. CONCLUSION: We identified significant correlations between LDD-characterized gut microbes and brain FC, as well as depression severity, which may contribute to the pathophysiology of depression development among patients with LLD. Specific microbes were linked to altered brain connectivity, suggesting potential targets for treating LLD.
背景：越来越多的证据表明，肠道微生物群在精神疾病（包括抑郁症）的发病机制中起着重要作用，这涉及到微生物群-肠道-大脑轴。我们试图探索老年抑郁症（LLD）患者肠道微生物组成与神经回路之间的相互作用。
方法：我们对老年抑郁症患者和健康对照者进行粪便 16S 核糖体 RNA（rRNA）测序和静息态功能磁共振成像，以描述肠道微生物群与脑功能连接（FC）之间的关联。我们使用汉密尔顿抑郁评定量表（HAMD）评估抑郁症状。
结果：我们纳入了 32 名老年抑郁症患者和 16 名健康对照者。在属水平上，与健康对照组相比，老年抑郁症患者中 、 、 、 和 的相对丰度显著更高。在抑郁患者中，主要在前脑皮层（例如右侧额上和额下回、右侧外侧枕叶、左侧额中回和左侧尾状核）内观察到情绪调节回路内的 FC 降低。在对照组和患者中，以组为特征的肠道微生物与基于种子的 FC 呈相反的相关性，这可能是老年抑郁症患者情绪调节异常的原因。 （在老年抑郁症患者中占优势的属）的丰度与 HAMD 评分（ = 0.49， = 0.0004）和组为特征的 FC（ = -0.37， < 0.05）均呈正相关，而 （在对照组中占优势的属）与 HAMD 评分（ = -0.30， = 0.04）和组为特征的 FC 均呈负相关。
局限性：该研究的横断面设计和小样本量限制了因果推断；需要更大的纵向研究进行详细的亚组分析。
结论：我们发现老年抑郁症患者肠道微生物与脑 FC 以及抑郁严重程度之间存在显著相关性，这可能有助于老年抑郁症患者抑郁发生的病理生理学。特定的微生物与改变的大脑连接有关，提示了治疗老年抑郁症的潜在靶点。
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