Cross-sectional analyses of metabolites across biological samples mediating dietary acid load and chronic kidney disease
Ilias Attaye,
Beverley Beynon-Cobb,
Panayiotis Louca,
Ana Nogal,
Alessia Visconti,
Francesca Tettamanzi,
Kari Wong,
Gregory Michellotti,
Tim D. Spector,
Mario Falchi,
Jordana T. Bell,
Cristina Menni
Affiliations
Ilias Attaye
Department of Twin Research, King’s College London, St Thomas' Hospital Campus, London SE1 7EH, UK; Amsterdam Cardiovascular Sciences, Diabetes & Metabolism, Amsterdam, the Netherlands; Corresponding author
Beverley Beynon-Cobb
Department of Twin Research, King’s College London, St Thomas' Hospital Campus, London SE1 7EH, UK; Department of Nutrition & Dietetics, University Hospitals Coventry & Warwickshire NHS Trust, Coventry CV2 2DX, UK
Panayiotis Louca
Department of Twin Research, King’s College London, St Thomas' Hospital Campus, London SE1 7EH, UK
Ana Nogal
Department of Twin Research, King’s College London, St Thomas' Hospital Campus, London SE1 7EH, UK
Alessia Visconti
Department of Twin Research, King’s College London, St Thomas' Hospital Campus, London SE1 7EH, UK
Francesca Tettamanzi
Department of Twin Research, King’s College London, St Thomas' Hospital Campus, London SE1 7EH, UK
Kari Wong
Metabolon, Research Triangle Park, Morrisville, NC 27560, USA
Gregory Michellotti
Metabolon, Research Triangle Park, Morrisville, NC 27560, USA
Tim D. Spector
Department of Twin Research, King’s College London, St Thomas' Hospital Campus, London SE1 7EH, UK
Mario Falchi
Department of Twin Research, King’s College London, St Thomas' Hospital Campus, London SE1 7EH, UK
Jordana T. Bell
Department of Twin Research, King’s College London, St Thomas' Hospital Campus, London SE1 7EH, UK
Cristina Menni
Department of Twin Research, King’s College London, St Thomas' Hospital Campus, London SE1 7EH, UK; Corresponding author
Summary: 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.
