Patients with end-stage renal disease (ESRD) are notably accompanied by cognitive disorder and anxiety or depressive symptom. We aimed to explore the linkages of the amygdala-based MR parameters, cognitive and mood performance, systematic inflammation and gut microbiota in ESRD. This prospective study enrolled 28 ESRD patients (13 males and 15 females, mean age of 43.9 ± 13.8 years) and 19 age- and sex-matched healthy control (HC) (12 males and 7 females, mean age of 44.1 ± 10.0 years). All subjects underwent cognitive assessment, inflammatory factor and stool microbiota analysis, and brain MRI analysis [amygdala-based functional connectivity and voxel-based morphometry (VBM)]. ERSD was separated by different microbiota strains. All factors were compared between ESRD and HC, as well as between ESRD subgroups. Pearson correlation analysis and causal mediation analysis were conducted to further investigate the relationship among the factors derived from the gut microbiota, brain and systemic inflammation. ESRD displayed gut dysbiosis and increased systemic inflammation when compared to HC (all P < 0.05). Meanwhile, ESRD showed smaller VBM in amygdala, decreased functional connectivity in left amygdala - right inferior parietal lobe [P < 0.05, Gaussian Random Field (GRF) corrected] and worse cognitive or mood performance. Moreover, ESRD-B (Prevutella mainly), when compared to ESRD-A (Bacteroides mainly), displayed increased interleukin-6, self-rating anxiety scale and functional connectivity in left amygdala - bilateral anterior cingulate cortex / medial superior frontal cortex (P < 0.05, GRF corrected). Furthermore, the correlation network of ESRD showed that both gut dysbiosis and amygdala-based alteration were correlated with cognitive performance and systemic inflammation. Causal mediation analysis validated that the disrupted distribution of Roseburia indirectly regulated the amygdala-based functional connectivity through tumor necrosis factor-alpha. The gut dysbiosis induced by ESRD was closely related to pro-inflammatory cytokines, amygdala-based phenotype, and mood performance. The lower abundance in Roseburia indirectly modulated amygdala-based functional connectivity pattern by tumor necrosis factor-alpha, which might provide a new way in diagnosis and treatment in patients of ESRD with depressive/anxious mood.

中文翻译：

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肠道生态失调对终末期肾病患者基于杏仁核的功能活动的影响：初步研究。

终末期肾病（ESRD）患者明显伴有认知障碍和焦虑或抑郁症状。我们的目的是探索 ESRD 中基于杏仁核的 MR 参数、认知和情绪表现、系统性炎症和肠道微生物群之间的联系。这项前瞻性研究招募了 28 名 ESRD 患者（13 名男性和 15 名女性，平均年龄 43.9 ± 13.8 岁）和 19 名年龄和性别匹配的健康对照（HC）（12 名男性和 7 名女性，平均年龄 44.1 ± 10.0 岁） . 所有受试者都接受了认知评估、炎症因子和粪便微生物群分析以及脑部 MRI 分析 [基于杏仁核的功能连接和基于体素的形态测量学 (VBM)]。ERSD 由不同的微生物群菌株分离。在 ESRD 和 HC 之间以及 ESRD 亚组之间比较了所有因素。进行了 Pearson 相关分析和因果中介分析，以进一步研究源自肠道微生物群、大脑和全身炎症的因素之间的关系。与 HC 相比，ESRD 表现出肠道生态失调和全身炎症增加（所有 P < 0.05）。同时，ESRD 显示杏仁核中的 VBM 较小，左侧杏仁核 - 右侧下顶叶的功能连接性降低 [P < 0.05，高斯随机场 (GRF) 校正] 以及更差的认知或情绪表现。此外，与 ESRD-A（主要是拟杆菌属）相比，ESRD-B（主要是普雷维特氏菌属）在左侧杏仁核 - 双侧前扣带皮层/内侧上额叶皮层（P < 0.05，GRF 校正）。此外，ESRD 的相关网络显示，肠道菌群失调和基于杏仁核的改变均与认知能力和全身炎症相关。因果中介分析证实，Roseburia 的破坏分布通过肿瘤坏死因子-α 间接调节了基于杏仁核的功能连接。ESRD 引起的肠道菌群失调与促炎细胞因子、基于杏仁核的表型和情绪表现密切相关。Roseburia 较低的丰度通过肿瘤坏死因子-α 间接调节基于杏仁核的功能连接模式，这可能为伴有抑郁/焦虑情绪的 ESRD 患者的诊断和治疗提供新的途径。因果中介分析证实，Roseburia 的破坏分布通过肿瘤坏死因子-α 间接调节了基于杏仁核的功能连接。ESRD 引起的肠道菌群失调与促炎细胞因子、基于杏仁核的表型和情绪表现密切相关。Roseburia 较低的丰度通过肿瘤坏死因子-α 间接调节基于杏仁核的功能连接模式，这可能为伴有抑郁/焦虑情绪的 ESRD 患者的诊断和治疗提供新的途径。因果中介分析证实，Roseburia 的破坏分布通过肿瘤坏死因子-α 间接调节了基于杏仁核的功能连接。ESRD 引起的肠道菌群失调与促炎细胞因子、基于杏仁核的表型和情绪表现密切相关。Roseburia 较低的丰度通过肿瘤坏死因子-α 间接调节基于杏仁核的功能连接模式，这可能为伴有抑郁/焦虑情绪的 ESRD 患者的诊断和治疗提供新的途径。和情绪表现。Roseburia 较低的丰度通过肿瘤坏死因子-α 间接调节基于杏仁核的功能连接模式，这可能为伴有抑郁/焦虑情绪的 ESRD 患者的诊断和治疗提供新的途径。和情绪表现。Roseburia 较低的丰度通过肿瘤坏死因子-α 间接调节基于杏仁核的功能连接模式，这可能为伴有抑郁/焦虑情绪的 ESRD 患者的诊断和治疗提供新的途径。