TY - JOUR
T1 - Metabolite profiles from multiple biological samples mediate the relationship between dietary acid load and mild chronic kidney disease: A cross-sectional study
AU - Attaye, Ilias
AU - Beynon-Cobb, Beverley
AU - Louca, Bano
AU - Nogal, Ana
AU - Visconti, Alessia
AU - Tettamanzi, Francesca
AU - Wong, Kari
AU - Michelotti, Gregory
AU - Spector, Tim
AU - Falchi, Mario
AU - Bell, Jordana
AU - Menni, Cristina
N1 - Funding Information:
This research was funded in whole, or in part, by the Wellcome Trust ( WT212904/Z/18/Z ). For the purpose of open access, the authors have applied a CC BY public copyright to any Author Accepted Manuscript version arising from this submission. The Department of Twin Research receives support from grants from the Wellcome Trust ( 212904/Z/18/Z ) and the Medical Research Council (MRC)/ British Heart Foundation (BHF) Ancestry and Biological Informative Markers for Stratification of Hypertension (AIM-HY; MR/M016560/1 ), European Union, Chronic Disease Research Foundation (CDRF), Zoe Global Ltd., and the NIHR Clinical Research Facility and Biomedical Research Centre (based at Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London). C.M. is funded by the Chronic Disease Research Foundation (CDRF), the UKRI grant ( MR/W026813/1 ), and the MRC /BHF (AIM-HY; MR/M016560/1 ). I.A. is funded by Amsterdam Cardiovascular Sciences Post-Doctoral grant . B.B.-C. is funded by a CRN West Midlands Personal Development Award and the Centre for Care Excellence at UHCW NHS Trust . P.L. is supported by the CDRF ( CDRF–15/2018 ). J.T.B. was supported by JPI ERA-HDHL-funded DIMENSION project through BBSRC ( BB/S020845/1 to J.T.B.). I.A. was funded through an Amsterdam Cardiovascular Sciences (ACS) post-doctoral grant ( 2022 ).
Funding Information:
We express our gratitude to all of the participants and staff at TwinsUK. This research was funded in whole, or in part, by the Wellcome Trust (WT212904/Z/18/Z). For the purpose of open access, the authors have applied a CC BY public copyright to any Author Accepted Manuscript version arising from this submission. The Department of Twin Research receives support from grants from the Wellcome Trust (212904/Z/18/Z) and the Medical Research Council (MRC)/British Heart Foundation (BHF) Ancestry and Biological Informative Markers for Stratification of Hypertension (AIM-HY; MR/M016560/1), European Union, Chronic Disease Research Foundation (CDRF), Zoe Global Ltd. and the NIHR Clinical Research Facility and Biomedical Research Centre (based at Guy's and St Thomas’ NHS Foundation Trust in partnership with King's College London). C.M. is funded by the Chronic Disease Research Foundation (CDRF), the UKRI grant (MR/W026813/1), and the MRC/BHF (AIM-HY; MR/M016560/1). I.A. is funded by Amsterdam Cardiovascular Sciences Post-Doctoral grant. B.B.-C. is funded by a CRN West Midlands Personal Development Award and the Centre for Care Excellence at UHCW NHS Trust. P.L. is supported by the CDRF (CDRF–15/2018). J.T.B. was supported by JPI ERA-HDHL-funded DIMENSION project through BBSRC (BB/S020845/1 to J.T.B.). I.A. was funded through an Amsterdam Cardiovascular Sciences (ACS) post-doctoral grant (2022). I.A. ran the analyses and verified the underlying data; I.A. B.B.-C. and C.M. wrote the original manuscript. P.L. A.N. F.T. A.V. K.W. G.M. M.F. and T.D.S. contributed methods/materials/analysis tools. All authors have read and approved the final version of the manuscript. T.D.S. is a co-founder and shareholder of ZOE Ltd.
Publisher Copyright:
© 2024 The Authors
PY - 2024/3/15
Y1 - 2024/3/15
N2 - Chronic kidney disease (CKD) is a major public health burden, with dietary acid load (DAL) and gut microbiota playing crucial roles. As DAL can affect the host metabolome, potentially via the gut microbiota, we cross-sectionally investigated the interplay between DAL, host metabolome, gut microbiota, and early-stage CKD (TwinsUK, n = 1,453). DAL was positively associated with CKD stage G1-G2 (Beta (95% confidence interval) = 0.34 (0.007; 0.7), p = 0.046). After adjusting for covariates and multiple testing, we identified 15 serum, 14 urine, 8 stool, and 7 saliva metabolites, primarily lipids and amino acids, associated with both DAL and CKD progression. Of these, 8 serum, 2 urine, and one stool metabolites were found to mediate the DAL-CKD association. Furthermore, the stool metabolite 5-methylhexanoate (i7:0) correlated with 26 gut microbial species. Our findings emphasize the gut microbiota's therapeutic potential in countering DAL's impact on CKD through the host metabolome. Interventional and longitudinal studies are needed to establish causality.
AB - Chronic kidney disease (CKD) is a major public health burden, with dietary acid load (DAL) and gut microbiota playing crucial roles. As DAL can affect the host metabolome, potentially via the gut microbiota, we cross-sectionally investigated the interplay between DAL, host metabolome, gut microbiota, and early-stage CKD (TwinsUK, n = 1,453). DAL was positively associated with CKD stage G1-G2 (Beta (95% confidence interval) = 0.34 (0.007; 0.7), p = 0.046). After adjusting for covariates and multiple testing, we identified 15 serum, 14 urine, 8 stool, and 7 saliva metabolites, primarily lipids and amino acids, associated with both DAL and CKD progression. Of these, 8 serum, 2 urine, and one stool metabolites were found to mediate the DAL-CKD association. Furthermore, the stool metabolite 5-methylhexanoate (i7:0) correlated with 26 gut microbial species. Our findings emphasize the gut microbiota's therapeutic potential in countering DAL's impact on CKD through the host metabolome. Interventional and longitudinal studies are needed to establish causality.
UR - http://www.scopus.com/inward/record.url?scp=85188211756&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2024.109132
DO - 10.1016/j.isci.2024.109132
M3 - Article
SN - 2589-0042
VL - 27
JO - iScience
JF - iScience
IS - 3
M1 - 109132
ER -
