TY - JOUR
T1 - Cross-sectional analyses of metabolites across biological samples mediating dietary acid load and chronic kidney disease
AU - Attaye, Ilias
AU - Beynon-Cobb, Beverley
AU - Louca, Panayiotis
AU - Nogal, Ana
AU - Visconti, Alessia
AU - Tettamanzi, Francesca
AU - Wong, Kari
AU - Michellotti, Gregory
AU - Spector, Tim D
AU - Falchi, Mario
AU - Bell, Jordana T
AU - Menni, Cristina
N1 - 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
C2 - 38433906
SN - 2589-0042
VL - 27
SP - 109132
JO - iScience
JF - iScience
IS - 3
M1 - 109132
ER -