Evaluating changes in firefighter urinary metabolomes after structural fires: an untargeted, high resolution approach
Abstract Firefighters have elevated rates of urinary tract cancers and other adverse health outcomes, which may be attributable to environmental occupational exposures. Untargeted metabolomics was applied to characterize this suite of environmental exposures and biological changes in response to occ...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-47799-x |
| _version_ | 1797415163412873216 |
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| author | Melissa A. Furlong Tuo Liu Justin M. Snider Malak M. Tfaily Christian Itson Shawn Beitel Krishna Parsawar Kristen Keck James Galligan Douglas I. Walker John J. Gulotta Jefferey L. Burgess |
| author_facet | Melissa A. Furlong Tuo Liu Justin M. Snider Malak M. Tfaily Christian Itson Shawn Beitel Krishna Parsawar Kristen Keck James Galligan Douglas I. Walker John J. Gulotta Jefferey L. Burgess |
| author_sort | Melissa A. Furlong |
| collection | DOAJ |
| description | Abstract Firefighters have elevated rates of urinary tract cancers and other adverse health outcomes, which may be attributable to environmental occupational exposures. Untargeted metabolomics was applied to characterize this suite of environmental exposures and biological changes in response to occupational firefighting. 200 urine samples from 100 firefighters collected at baseline and two to four hours post-fire were analyzed using untargeted liquid-chromatography and high-resolution mass spectrometry. Changes in metabolite abundance after a fire were estimated with fixed effects linear regression, with false discovery rate (FDR) adjustment. Partial least squares discriminant analysis (PLS-DA) was also used, and variable important projection (VIP) scores were extracted. Systemic changes were evaluated using pathway enrichment for highly discriminating metabolites. Metabolome-wide-association-study (MWAS) identified 268 metabolites associated with firefighting activity at FDR q < 0.05. Of these, 20 were annotated with high confidence, including the amino acids taurine, proline, and betaine; the indoles kynurenic acid and indole-3-acetic acid; the known uremic toxins trimethylamine n-oxide and hippuric acid; and the hormone 7a-hydroxytestosterone. Partial least squares discriminant analysis (PLS-DA) additionally implicated choline, cortisol, and other hormones. Significant pathways included metabolism of urea cycle/amino group, alanine and aspartate, aspartate and asparagine, vitamin b3 (nicotinate and nicotinamide), and arginine and proline. Firefighters show a broad metabolic response to fires, including altered excretion of indole compounds and uremic toxins. Implicated pathways and features, particularly uremic toxins, may be important regulators of firefighter’s increased risk for urinary tract cancers. |
| first_indexed | 2024-03-09T05:44:53Z |
| format | Article |
| id | doaj.art-2fb896ec49dc41b2b3c1c7792671071d |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-09T05:44:53Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-2fb896ec49dc41b2b3c1c7792671071d2023-12-03T12:21:56ZengNature PortfolioScientific Reports2045-23222023-11-0113111210.1038/s41598-023-47799-xEvaluating changes in firefighter urinary metabolomes after structural fires: an untargeted, high resolution approachMelissa A. Furlong0Tuo Liu1Justin M. Snider2Malak M. Tfaily3Christian Itson4Shawn Beitel5Krishna Parsawar6Kristen Keck7James Galligan8Douglas I. Walker9John J. Gulotta10Jefferey L. Burgess11Environmental Health Sciences, Mel and Enid Zuckerman College of Public Health, University of ArizonaEnvironmental Health Sciences, Mel and Enid Zuckerman College of Public Health, University of ArizonaSchool of Nutritional Sciences and Wellness, University of ArizonaDepartment of Environmental Science, University of ArizonaDepartment of Environmental Science, University of ArizonaEnvironmental Health Sciences, Mel and Enid Zuckerman College of Public Health, University of ArizonaAnalytical and Biological Mass Spectrometry Core, University of ArizonaAnalytical and Biological Mass Spectrometry Core, University of ArizonaCollege of Pharmacy, University of ArizonaGangarosa Department of Environmental Health, Emory University Rollins School of Public HealthTucson Fire DepartmentEnvironmental Health Sciences, Mel and Enid Zuckerman College of Public Health, University of ArizonaAbstract Firefighters have elevated rates of urinary tract cancers and other adverse health outcomes, which may be attributable to environmental occupational exposures. Untargeted metabolomics was applied to characterize this suite of environmental exposures and biological changes in response to occupational firefighting. 200 urine samples from 100 firefighters collected at baseline and two to four hours post-fire were analyzed using untargeted liquid-chromatography and high-resolution mass spectrometry. Changes in metabolite abundance after a fire were estimated with fixed effects linear regression, with false discovery rate (FDR) adjustment. Partial least squares discriminant analysis (PLS-DA) was also used, and variable important projection (VIP) scores were extracted. Systemic changes were evaluated using pathway enrichment for highly discriminating metabolites. Metabolome-wide-association-study (MWAS) identified 268 metabolites associated with firefighting activity at FDR q < 0.05. Of these, 20 were annotated with high confidence, including the amino acids taurine, proline, and betaine; the indoles kynurenic acid and indole-3-acetic acid; the known uremic toxins trimethylamine n-oxide and hippuric acid; and the hormone 7a-hydroxytestosterone. Partial least squares discriminant analysis (PLS-DA) additionally implicated choline, cortisol, and other hormones. Significant pathways included metabolism of urea cycle/amino group, alanine and aspartate, aspartate and asparagine, vitamin b3 (nicotinate and nicotinamide), and arginine and proline. Firefighters show a broad metabolic response to fires, including altered excretion of indole compounds and uremic toxins. Implicated pathways and features, particularly uremic toxins, may be important regulators of firefighter’s increased risk for urinary tract cancers.https://doi.org/10.1038/s41598-023-47799-x |
| spellingShingle | Melissa A. Furlong Tuo Liu Justin M. Snider Malak M. Tfaily Christian Itson Shawn Beitel Krishna Parsawar Kristen Keck James Galligan Douglas I. Walker John J. Gulotta Jefferey L. Burgess Evaluating changes in firefighter urinary metabolomes after structural fires: an untargeted, high resolution approach Scientific Reports |
| title | Evaluating changes in firefighter urinary metabolomes after structural fires: an untargeted, high resolution approach |
| title_full | Evaluating changes in firefighter urinary metabolomes after structural fires: an untargeted, high resolution approach |
| title_fullStr | Evaluating changes in firefighter urinary metabolomes after structural fires: an untargeted, high resolution approach |
| title_full_unstemmed | Evaluating changes in firefighter urinary metabolomes after structural fires: an untargeted, high resolution approach |
| title_short | Evaluating changes in firefighter urinary metabolomes after structural fires: an untargeted, high resolution approach |
| title_sort | evaluating changes in firefighter urinary metabolomes after structural fires an untargeted high resolution approach |
| url | https://doi.org/10.1038/s41598-023-47799-x |
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