A phenome-wide association study (PheWAS) to identify the health impacts of 4-cresol sulfate in the Nagahama Study.

Autor: Ou H; Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan.; Department of Human Genetics, McGill University, Montreal, QC, H3A 0C7, Canada., Kawaguchi S; Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan., Sonomura K; Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan.; Life Science Research Center, Technology Research Laboratory, Shimadzu Corporation, Kyoto, 604-8511, Japan., Kawaguchi T; Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan., Kitada S; Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan., Yoshiji S; Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan.; Department of Human Genetics, McGill University, Montreal, QC, H3A 0C7, Canada., Brial F; Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan., Gauguier D; Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan.; Department of Human Genetics, McGill University, Montreal, QC, H3A 0C7, Canada.; University Paris Cité, INSERM UMR1124, 45 rue des Saints Peres, 75006, Paris, France., Xia J; Department of Human Genetics, McGill University, Montreal, QC, H3A 0C7, Canada.; Institute of Parasitology, McGill University, Montreal, QC, H9X 3V9, Canada., Matsuda F; Center for Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan. fumi@genome.med.kyoto-u.ac.jp.; Department of Human Genetics, McGill University, Montreal, QC, H3A 0C7, Canada. fumi@genome.med.kyoto-u.ac.jp.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 Aug 25; Vol. 13 (1), pp. 13926. Date of Electronic Publication: 2023 Aug 25.
DOI: 10.1038/s41598-023-40697-2
Abstrakt: Gut-microbiota derived metabolites are important regulators of host biology and metabolism. To understand the impacts of the microbial metabolite 4-cresol sulfate (4-CS) on four chronic diseases [type 2 diabetes mellitus, metabolic syndrome (MetS), non-alcoholic fatty liver disease, and chronic kidney disease (CKD)], we conducted association analyses of plasma 4-CS quantified by liquid chromatography coupled to mass spectrometry (LC-MS) in 3641 participants of the Nagahama study. Our results validated the elevation of 4-CS in CKD and identified a reducing trend in MetS. To delineate the holistic effects of 4-CS, we performed a phenome-wide association analysis (PheWAS) with 937 intermediate biological and behavioral traits. We detected associations between 4-CS and 39 phenotypes related to blood pressure regulation, hepatic and renal functions, hematology, sleep quality, intraocular pressure, ion regulation, ketone and fatty acid metabolisms, disease history and dietary habits. Among them, 19 PheWAS significant traits, including fatty acids and 14 blood pressure indices, were correlated with MetS, suggesting that 4-CS is a potential biomarker for MetS. Consistent associations of this gut microbial-derived metabolite on multiple endophenotypes underlying distinct etiopathogenesis support its role in the overall host health, with prospects of probiotic-based therapeutic solutions in chronic diseases.
(© 2023. Springer Nature Limited.)
Databáze: MEDLINE
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