Metabolic Features of Increased Gut Permeability, Inflammation, and Altered Energy Metabolism Distinguish Agricultural Workers at Risk for Mesoamerican Nephropathy
Mesoamerican nephropathy (MeN) is a form of chronic kidney disease found predominantly in young men in Mesoamerica. Strenuous agricultural labor is a consistent risk factor for MeN, but the pathophysiologic mechanism leading to disease is poorly understood. We compared the urine metabolome among men...
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MDPI AG
2023-02-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/13/3/325 |
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| author | Nathan H. Raines Dominick A. Leone Cristina O’Callaghan-Gordo Oriana Ramirez-Rubio Juan José Amador Damaris Lopez Pilarte Iris S. Delgado Jessica H. Leibler Nieves Embade Rubén Gil-Redondo Chiara Bruzzone Maider Bizkarguenaga Madeleine K. Scammell Samir M. Parikh Oscar Millet Daniel R. Brooks David J. Friedman |
| author_facet | Nathan H. Raines Dominick A. Leone Cristina O’Callaghan-Gordo Oriana Ramirez-Rubio Juan José Amador Damaris Lopez Pilarte Iris S. Delgado Jessica H. Leibler Nieves Embade Rubén Gil-Redondo Chiara Bruzzone Maider Bizkarguenaga Madeleine K. Scammell Samir M. Parikh Oscar Millet Daniel R. Brooks David J. Friedman |
| author_sort | Nathan H. Raines |
| collection | DOAJ |
| description | Mesoamerican nephropathy (MeN) is a form of chronic kidney disease found predominantly in young men in Mesoamerica. Strenuous agricultural labor is a consistent risk factor for MeN, but the pathophysiologic mechanism leading to disease is poorly understood. We compared the urine metabolome among men in Nicaragua engaged in sugarcane harvest and seed cutting (<i>n</i> = 117), a group at high risk for MeN, against three referents: Nicaraguans working less strenuous jobs at the same sugarcane plantations (<i>n</i> = 78); Nicaraguans performing non-agricultural work (<i>n</i> = 102); and agricultural workers in Spain (<i>n</i> = 78). Using proton nuclear magnetic resonance, we identified 136 metabolites among participants. Our non-hypothesis-based approach identified distinguishing urine metabolic features in the high-risk group, revealing increased levels of hippurate and other gut-derived metabolites and decreased metabolites related to central energy metabolism when compared to referent groups. Our complementary hypothesis-based approach, focused on nicotinamide adenine dinucleotide (NAD+) related metabolites, and revealed a higher kynurenate/tryptophan ratio in the high-risk group (<i>p</i> = 0.001), consistent with a heightened inflammatory state. Workers in high-risk occupations are distinguishable by urinary metabolic features that suggest increased gut permeability, inflammation, and altered energy metabolism. Further study is needed to explore the pathophysiologic implications of these findings. |
| first_indexed | 2024-03-11T06:11:09Z |
| format | Article |
| id | doaj.art-354e1c3725e24c41ba2f6844276d48e9 |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-11T06:11:09Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-354e1c3725e24c41ba2f6844276d48e92023-11-17T12:35:55ZengMDPI AGMetabolites2218-19892023-02-0113332510.3390/metabo13030325Metabolic Features of Increased Gut Permeability, Inflammation, and Altered Energy Metabolism Distinguish Agricultural Workers at Risk for Mesoamerican NephropathyNathan H. Raines0Dominick A. Leone1Cristina O’Callaghan-Gordo2Oriana Ramirez-Rubio3Juan José Amador4Damaris Lopez Pilarte5Iris S. Delgado6Jessica H. Leibler7Nieves Embade8Rubén Gil-Redondo9Chiara Bruzzone10Maider Bizkarguenaga11Madeleine K. Scammell12Samir M. Parikh13Oscar Millet14Daniel R. Brooks15David J. Friedman16Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USADepartment of Epidemiology, Boston University School of Public Health, Boston, MA 02118, USAFaculty of Health Sciences, Universitat Oberta de Catalunya, 08018 Barcelona, SpainDepartment of Epidemiology, Boston University School of Public Health, Boston, MA 02118, USADepartment of Epidemiology, Boston University School of Public Health, Boston, MA 02118, USADepartment of Epidemiology, Boston University School of Public Health, Boston, MA 02118, USADepartment of Epidemiology, Boston University School of Public Health, Boston, MA 02118, USADepartment of Environmental Health, Boston University School of Public Health, Boston, MA 02118, USAPrecision Medicine and Metabolism Laboratory, CIC bioGUNE, Basque Research and Technology Alliance (BRTA), 48160 Derio, SpainPrecision Medicine and Metabolism Laboratory, CIC bioGUNE, Basque Research and Technology Alliance (BRTA), 48160 Derio, SpainPrecision Medicine and Metabolism Laboratory, CIC bioGUNE, Basque Research and Technology Alliance (BRTA), 48160 Derio, SpainPrecision Medicine and Metabolism Laboratory, CIC bioGUNE, Basque Research and Technology Alliance (BRTA), 48160 Derio, SpainDepartment of Epidemiology, Boston University School of Public Health, Boston, MA 02118, USADivision of Nephrology, Department of Medicine, University of Texas Southwestern Medical School, Dallas, TX 75390, USAPrecision Medicine and Metabolism Laboratory, CIC bioGUNE, Basque Research and Technology Alliance (BRTA), 48160 Derio, SpainDepartment of Epidemiology, Boston University School of Public Health, Boston, MA 02118, USADivision of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USAMesoamerican nephropathy (MeN) is a form of chronic kidney disease found predominantly in young men in Mesoamerica. Strenuous agricultural labor is a consistent risk factor for MeN, but the pathophysiologic mechanism leading to disease is poorly understood. We compared the urine metabolome among men in Nicaragua engaged in sugarcane harvest and seed cutting (<i>n</i> = 117), a group at high risk for MeN, against three referents: Nicaraguans working less strenuous jobs at the same sugarcane plantations (<i>n</i> = 78); Nicaraguans performing non-agricultural work (<i>n</i> = 102); and agricultural workers in Spain (<i>n</i> = 78). Using proton nuclear magnetic resonance, we identified 136 metabolites among participants. Our non-hypothesis-based approach identified distinguishing urine metabolic features in the high-risk group, revealing increased levels of hippurate and other gut-derived metabolites and decreased metabolites related to central energy metabolism when compared to referent groups. Our complementary hypothesis-based approach, focused on nicotinamide adenine dinucleotide (NAD+) related metabolites, and revealed a higher kynurenate/tryptophan ratio in the high-risk group (<i>p</i> = 0.001), consistent with a heightened inflammatory state. Workers in high-risk occupations are distinguishable by urinary metabolic features that suggest increased gut permeability, inflammation, and altered energy metabolism. Further study is needed to explore the pathophysiologic implications of these findings.https://www.mdpi.com/2218-1989/13/3/325Mesoamerican nephropathy (MeN)chronic kidney disease of unknown etiology (CKDu)chronic kidney disease of nontraditional cause (CKDnt)nicotinamide adenine dinucleotide (NAD+)kynurenatetryptophan |
| spellingShingle | Nathan H. Raines Dominick A. Leone Cristina O’Callaghan-Gordo Oriana Ramirez-Rubio Juan José Amador Damaris Lopez Pilarte Iris S. Delgado Jessica H. Leibler Nieves Embade Rubén Gil-Redondo Chiara Bruzzone Maider Bizkarguenaga Madeleine K. Scammell Samir M. Parikh Oscar Millet Daniel R. Brooks David J. Friedman Metabolic Features of Increased Gut Permeability, Inflammation, and Altered Energy Metabolism Distinguish Agricultural Workers at Risk for Mesoamerican Nephropathy Metabolites Mesoamerican nephropathy (MeN) chronic kidney disease of unknown etiology (CKDu) chronic kidney disease of nontraditional cause (CKDnt) nicotinamide adenine dinucleotide (NAD+) kynurenate tryptophan |
| title | Metabolic Features of Increased Gut Permeability, Inflammation, and Altered Energy Metabolism Distinguish Agricultural Workers at Risk for Mesoamerican Nephropathy |
| title_full | Metabolic Features of Increased Gut Permeability, Inflammation, and Altered Energy Metabolism Distinguish Agricultural Workers at Risk for Mesoamerican Nephropathy |
| title_fullStr | Metabolic Features of Increased Gut Permeability, Inflammation, and Altered Energy Metabolism Distinguish Agricultural Workers at Risk for Mesoamerican Nephropathy |
| title_full_unstemmed | Metabolic Features of Increased Gut Permeability, Inflammation, and Altered Energy Metabolism Distinguish Agricultural Workers at Risk for Mesoamerican Nephropathy |
| title_short | Metabolic Features of Increased Gut Permeability, Inflammation, and Altered Energy Metabolism Distinguish Agricultural Workers at Risk for Mesoamerican Nephropathy |
| title_sort | metabolic features of increased gut permeability inflammation and altered energy metabolism distinguish agricultural workers at risk for mesoamerican nephropathy |
| topic | Mesoamerican nephropathy (MeN) chronic kidney disease of unknown etiology (CKDu) chronic kidney disease of nontraditional cause (CKDnt) nicotinamide adenine dinucleotide (NAD+) kynurenate tryptophan |
| url | https://www.mdpi.com/2218-1989/13/3/325 |
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