Theranostics 2019; 9(26):8171-8181. doi:10.7150/thno.35387

Research Paper

The gut microbiota-inflammation-brain axis in end-stage renal disease: perspectives from default mode network

Yun Fei Wang1, Li Juan Zheng1, Ya Liu1, Yu Bing Ye1, Song Luo1, Guang Ming Lu1, Dehua Gong2, Long Jiang Zhang1✉

1. Department of Medical Imaging, Medical Imaging Center, Jinling Hospital, Medical School of Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nanjing, Jiangsu Province, 210002, China.
2. National Clinical Research Center of Kidney Disease, Jinling Hospital, Medical School of Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nanjing, Jiangsu Province, 210002, China.

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Citation:
Wang YF, Zheng LJ, Liu Y, Ye YB, Luo S, Lu GM, Gong D, Zhang LJ. The gut microbiota-inflammation-brain axis in end-stage renal disease: perspectives from default mode network. Theranostics 2019; 9(26):8171-8181. doi:10.7150/thno.35387. Available from http://www.thno.org/v09p8171.htm

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Abstract

The gut-brain axis in end-stage renal disease (ESRD) is attracting more and more attention. However, the mechanism of gut-brain axis based cognitive disorders in ESRD patients remains unclear. The purpose of this study was to investigate the linkages between the gut microbiota, inflammatory cytokines, brain default mode network (DMN) and cognitive function in ESRD patients.

Methods: This prospective study enrolled 28 ESRD patients (13 males and 15 females, mean age of 44 ± 14 years) and 19 healthy controls (HCs) (12 males and 7 females, mean age of 44 ± 10 years). All subjects underwent stool microbiota analysis, blood inflammatory cytokines examination, brain MRI scans and cognitive assessments. Resting state functional MRI (rs-fMRI) data were used to construct DMN and graph theory was applied to characterize network topological properties. Two samples t-test was applied for the comparisons between ESRD and HCs. Correlation analysis and mediation analysis were conducted among factors with significant group differences.

Results: ESRD patients displayed gut microbiota alterations, increased systemic inflammation and worse cognitive performance compared to HCs (all p < 0.05). Graph analysis revealed disrupted DMN topological organization, aberrant nodal centralities and functional connectivities (FCs) in ESRD patients relative to HCs (all p < 0.05, FDR corrected). Significant correlations were found between gut microbiota, inflammatory cytokines, DMN network measures and cognitive assessments. Mediation analysis found that gut microbiota alteration impaired DMN connectivity by increasing systemic inflammation.

Conclusion: The present study first revealed gut microbiota alterations, systemic inflammation, DMN dissociation and cognitive dysfunction in ESRD patients simultaneously and further illuminated their inner relationship.

Keywords: end-stage renal disease, gut microbiota, default mode network, inflammatory cytokine, resting state fMRI