A normative microbiome is not restored following kidney transplantation

Craven, H., Erlandsson, H., McGuinness, D., McGuinness, D. , Mafra, D., Ijaz, U. Z. , Bergman, P., Shiels, P. G. and Stenvinkel, P. (2023) A normative microbiome is not restored following kidney transplantation. Clinical Science, 137(20), pp. 1563-1575. (doi: 10.1042/CS20230779) (PMID:37756543)

Abstract

Dialysis and kidney transplantation (Ktx) mitigate some of the physiological deficits in chronic kidney disease (CKD), but it remains to be determined if these mitigate microbial dysbiosis and the production of inflammatory microbial metabolites, which contribute significantly to the uraemic phenotype. We have investigated bacterial DNA signatures present in the circulation of CKD patients and those receiving a KTx. Our data are consistent with increasing dysbiosis as CKD progresses, with an accompanying increase in trimethylamine (TMA) producing pathobionts Pseudomonas and Bacillus. Notably, KTx patients displayed a significantly different microbiota compared to CKD5 patients, which surprisingly included further increase in TMA producing Bacillus and loss of salutogenic Lactobacilli. Only two genera (Viellonella and Saccharimonidales) showed significant differences in abundance following KTx that may reflect a reciprocal relationship between TMA producers and utilisers, which supersedes restoration of a normative microbiome. Our metadata analysis confirmed that TMA N-oxide along with one carbon metabolism, had significant impact upon both inflammatory burden and the composition of the microbiome. This indicates that these metabolites are key to shaping the uraemic microbiome and might be exploited in the development of dietary intervention strategies to both mitigate the physiological deficits in CKD and enable the restoration of a more salutogenic microbiome.

• Item Type: Articles
• Additional Information: Funding provided by Swedish Medical Research Council, CIMED and Heart and Lung Foundation.
• Keywords: Microbiome, CKD, kidney transplant, TMAO.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McGuinness, Dr Dagmara and Mcguinness, Dr David and Shiels, Professor Paul and Ijaz, Dr Umer and Craven, Hannah

Creator Roles

Craven, H.: Data curation, Software, Formal analysis, Validation, Investigation, Visualization, Methodology, Writing – original draft
McGuinness, D.: Data curation, Formal analysis, Investigation, Methodology, Writing – review and editing
Mcguinness, D.: Resources, Data curation, Formal analysis, Investigation, Writing – review and editing
Ijaz, U.: Resources, Data curation, Formal analysis, Investigation, Writing – review and editing
Shiels, P.: Conceptualization, Resources, Data curation, Software, Formal analysis, Supervision, Funding acquisition, Validation, Investigation, Visualization, Methodology, Writing – original draft, Project administration, Writing – review and editing

• Authors: Craven, H., Erlandsson, H., McGuinness, D., McGuinness, D., Mafra, D., Ijaz, U. Z., Bergman, P., Shiels, P. G., and Stenvinkel, P.
• College/School: College of Medical Veterinary and Life Sciences; College of Medical Veterinary and Life Sciences > School of Cancer Sciences; College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Molecular Biosciences; College of Science and Engineering > School of Engineering > Infrastructure and Environment
• Journal Name: Clinical Science
• Publisher: Portland Press
• ISSN: 0143-5221
• ISSN (Online): 1470-8736
• Published Online: 27 September 2023
• Copyright Holders: Copyright © 2023 The Author(s)
• First Published: First published in Clinical Science 137(20):1563–1575.
• Publisher Policy: Reproduced under a Creative Commons licence