Abnormalities in Gut Microbiota and Serum Metabolites in Hemodialysis Patients with Mild Cognitive Decline: A Single-Center Observational Study

Background: Although accumulating evidence indicates that the cognitive function scores are significantly lower in hemodialysis patients than in healthy individuals, the underlying mechanisms have not been fully elucidated. This prospective observational study aimed to investigate the role of gut microbiota and serum metabolites in hemodialysis patients with mild cognitive decline (MCD). Methods: A total of 30 healthy individuals and 77 hemodialysis patients were classified into healthy control (HC), normal cognitive function (NCF), and MCD groups based on evaluation by the Montreal Cognitive Assessment (MoCA). 16S rRNA sequencing and Metabolomics analysis were used to determine the alteration of gut microbiota profiles and serum metabolites among MCD, HC and NCF groups. Findings: The gut microbiota profiles, including α and β diversities and the number of 16 gut bacterial species, were significantly altered in the MCD group compared with the HC and the NCF groups. Metabolomics analysis showed that the levels of 29 serum metabolites were altered in the MCD group. Receiver operating characteristic (ROC) curves revealed the genus Bilophila and serum putrescine as potential sensitive biomarkers for detecting MCD in patients undergoing hemodialysis. Interpretation: These results suggest the potential role of gut microbiota and serum metabolites in the pathogenesis of hemodialysis-related MCD. Therapeutic strategies targeting abnormalities in gut microbiota and serum metabolites may facilitate the beneficial effects for hemodialysis patients with MCD. Trial Registration: This clinical study was registered with the Chinese Clinical Trial Register (clinical trial number: ChiCTR-ROC-16009283). Funding Statement: This study was supported by grants from the National Natural Science Foundation of China (to A.L., 81771159 and 81571047; to C.Y., 81703482) and was partially supported by the Program of Bureau of Science and Technology Foundation of Changzhou (to B.Z., CJ20159022; to L.M., CJ20179028) and Major Science and Technology Projects of Changzhou Municipal Committee of Health and Family Planning (to B.Z., ZD201505; to L.M., ZD201601). Declaration of Interests: All the authors declared no conflicts of interest. Ethics Approval Statement: Written informed consent was obtained from all participants, and the study was approved by the Ethics Commission of The Third Affiliated Hospital of Soochow University (Changzhou, China) and conducted in accordance with the principles of the Declaration of Helsinki. The data of a subset of patients were reported in a previous study.