A phenome-wide association study (PheWAS) to identify the health impacts of 4-cresol sulfate in the Nagahama Study
Abstract 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 chr...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-40697-2 |
| _version_ | 1797560186489012224 |
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| author | Huiting Ou Shuji Kawaguchi Kazuhiro Sonomura Takahisa Kawaguchi Seri Kitada Satoshi Yoshiji François Brial Dominique Gauguier Jianguo Xia Fumihiko Matsuda |
| author_facet | Huiting Ou Shuji Kawaguchi Kazuhiro Sonomura Takahisa Kawaguchi Seri Kitada Satoshi Yoshiji François Brial Dominique Gauguier Jianguo Xia Fumihiko Matsuda |
| author_sort | Huiting Ou |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-10T17:55:50Z |
| format | Article |
| id | doaj.art-4afe2ec4a5a647b29e0a385de7c55238 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-10T17:55:50Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-4afe2ec4a5a647b29e0a385de7c552382023-11-20T09:10:53ZengNature PortfolioScientific Reports2045-23222023-08-011311910.1038/s41598-023-40697-2A phenome-wide association study (PheWAS) to identify the health impacts of 4-cresol sulfate in the Nagahama StudyHuiting Ou0Shuji Kawaguchi1Kazuhiro Sonomura2Takahisa Kawaguchi3Seri Kitada4Satoshi Yoshiji5François Brial6Dominique Gauguier7Jianguo Xia8Fumihiko Matsuda9Center for Genomic Medicine, Graduate School of Medicine, Kyoto UniversityCenter for Genomic Medicine, Graduate School of Medicine, Kyoto UniversityCenter for Genomic Medicine, Graduate School of Medicine, Kyoto UniversityCenter for Genomic Medicine, Graduate School of Medicine, Kyoto UniversityCenter for Genomic Medicine, Graduate School of Medicine, Kyoto UniversityCenter for Genomic Medicine, Graduate School of Medicine, Kyoto UniversityCenter for Genomic Medicine, Graduate School of Medicine, Kyoto UniversityCenter for Genomic Medicine, Graduate School of Medicine, Kyoto UniversityDepartment of Human Genetics, McGill UniversityCenter for Genomic Medicine, Graduate School of Medicine, Kyoto UniversityAbstract 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.https://doi.org/10.1038/s41598-023-40697-2 |
| spellingShingle | Huiting Ou Shuji Kawaguchi Kazuhiro Sonomura Takahisa Kawaguchi Seri Kitada Satoshi Yoshiji François Brial Dominique Gauguier Jianguo Xia Fumihiko Matsuda A phenome-wide association study (PheWAS) to identify the health impacts of 4-cresol sulfate in the Nagahama Study Scientific Reports |
| title | A phenome-wide association study (PheWAS) to identify the health impacts of 4-cresol sulfate in the Nagahama Study |
| title_full | A phenome-wide association study (PheWAS) to identify the health impacts of 4-cresol sulfate in the Nagahama Study |
| title_fullStr | A phenome-wide association study (PheWAS) to identify the health impacts of 4-cresol sulfate in the Nagahama Study |
| title_full_unstemmed | A phenome-wide association study (PheWAS) to identify the health impacts of 4-cresol sulfate in the Nagahama Study |
| title_short | A phenome-wide association study (PheWAS) to identify the health impacts of 4-cresol sulfate in the Nagahama Study |
| title_sort | phenome wide association study phewas to identify the health impacts of 4 cresol sulfate in the nagahama study |
| url | https://doi.org/10.1038/s41598-023-40697-2 |
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