Abstract
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.
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Abbreviations
- ACC:
-
anterior cingulate cortex
- CKD:
-
chronic kidney disease
- ESRD:
-
end-stage renal disease
- HC:
-
healthy control
- IFN-gamma:
-
interferon-gamma
- IL:
-
interleukin
- IPL:
-
inferior parietal lobe
- MMSE:
-
Mini-Mental State Examination
- MoCA:
-
Montreal Cognitive Assessment Scale
- MSFC:
-
medial superior frontal cortex
- NCT-A:
-
Number Connection Test type-A
- rs-fMRI:
-
resting-state functional magnetic resonance imaging
- SAS:
-
self-rating anxiety scale
- SDS:
-
self-rating depression scale
- SDT:
-
serial dotting test
- TNF-alpha:
-
tumor necrosis factor-alpha
- VBM:
-
voxel-based morphometry
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The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
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This work was supported by the grants from the Natural Scientific Foundation of China (81,322,020 and 81,230,032 to Long Jiang Zheng; 81,801,686 to Li Juan Zheng).
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LJZ, GL and DG conceived and designed the experiments. LJ, LL, ZHZ, YFW, YBY, YL and XYZ performed the experiments. LJ, LL, JZ, YL, and LJZ analyzed the data and wrote the paper. All authors read and approved the final manuscript.
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Zheng, L.J., Lin, L., Zhong, J. et al. Gut dysbiosis-influence on amygdala-based functional activity in patients with end stage renal disease: a preliminary study. Brain Imaging and Behavior 14, 2731–2744 (2020). https://doi.org/10.1007/s11682-019-00223-3
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DOI: https://doi.org/10.1007/s11682-019-00223-3