Exposure to environmental toxicants is associated with gut microbiome dysbiosis, insulin resistance and obesity
Environmental toxicants (ETs) are associated with adverse health outcomes. Here we hypothesized that exposures to ETs are linked with obesity and insulin resistance partly through a dysbiotic gut microbiota and changes in the serum levels of secondary bile acids (BAs). Serum BAs, per- and polyfluoro...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-04-01
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| Series: | Environment International |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0160412024001557 |
| _version_ | 1797246900667154432 |
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| author | Partho Sen Yong Fan Jennifer J. Schlezinger Stanislav D. Ehrlich Thomas F. Webster Tuulia Hyötyläinen Oluf Pedersen Matej Orešič |
| author_facet | Partho Sen Yong Fan Jennifer J. Schlezinger Stanislav D. Ehrlich Thomas F. Webster Tuulia Hyötyläinen Oluf Pedersen Matej Orešič |
| author_sort | Partho Sen |
| collection | DOAJ |
| description | Environmental toxicants (ETs) are associated with adverse health outcomes. Here we hypothesized that exposures to ETs are linked with obesity and insulin resistance partly through a dysbiotic gut microbiota and changes in the serum levels of secondary bile acids (BAs). Serum BAs, per- and polyfluoroalkyl substances (PFAS) and additional twenty-seven ETs were measured by mass spectrometry in 264 Danes (121 men and 143 women, aged 56.6 ± 7.3 years, BMI 29.7 ± 6.0 kg/m2) using a combination of targeted and suspect screening approaches. Bacterial species were identified based on whole-genome shotgun sequencing (WGS) of DNA extracted from stool samples. Personalized genome-scale metabolic models (GEMs) of gut microbial communities were developed to elucidate regulation of BA pathways. Subsequently, we compared findings from the human study with metabolic implications of exposure to perfluorooctanoic acid (PFOA) in PPARα-humanized mice. Serum levels of twelve ETs were associated with obesity and insulin resistance. High chemical exposure was associated with increased abundance of several bacterial species (spp.) of genus (Anaerotruncus, Alistipes, Bacteroides, Bifidobacterium, Clostridium, Dorea, Eubacterium, Escherichia, Prevotella, Ruminococcus, Roseburia, Subdoligranulum, and Veillonella), particularly in men. Conversely, females in the higher exposure group, showed a decrease abundance of Prevotella copri. High concentrations of ETs were correlated with increased levels of secondary BAs including lithocholic acid (LCA), and decreased levels of ursodeoxycholic acid (UDCA). In silico causal inference analyses suggested that microbiome-derived secondary BAs may act as mediators between ETs and obesity or insulin resistance. Furthermore, these findings were substantiated by the outcome of the murine exposure study. Our combined epidemiological and mechanistic studies suggest that multiple ETs may play a role in the etiology of obesity and insulin resistance. These effects may arise from disruptions in the microbial biosynthesis of secondary BAs. |
| first_indexed | 2024-04-24T19:50:09Z |
| format | Article |
| id | doaj.art-f376be16f4364257b24a48f878d043eb |
| institution | Directory Open Access Journal |
| issn | 0160-4120 |
| language | English |
| last_indexed | 2024-04-24T19:50:09Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Environment International |
| spelling | doaj.art-f376be16f4364257b24a48f878d043eb2024-03-25T04:17:06ZengElsevierEnvironment International0160-41202024-04-01186108569Exposure to environmental toxicants is associated with gut microbiome dysbiosis, insulin resistance and obesityPartho Sen0Yong Fan1Jennifer J. Schlezinger2Stanislav D. Ehrlich3Thomas F. Webster4Tuulia Hyötyläinen5Oluf Pedersen6Matej Orešič7Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520, Turku, Finland; School of Medical Sciences, Faculty of Medicine and Health, Örebro University, 702 81, Örebro, SwedenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, DenmarkDepartment of Environmental Health, Boston University School of Public Health, Boston, MA, USADepartment of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London WC1N 3RX, UKDepartment of Environmental Health, Boston University School of Public Health, Boston, MA, USAMTM Research Centre, School of Science and Technology, Örebro University, 702 81, Örebro, Sweden; Corresponding authors at: School of Medical Sciences, Örebro University, Örebro, Sweden.Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark; Center for Clinical Metabolic Research, Herlev-Gentofte University Hospital, Copenhagen, Denmark; Corresponding authors at: School of Medical Sciences, Örebro University, Örebro, Sweden.Turku Bioscience Centre, University of Turku and Åbo Akademi University, 20520, Turku, Finland; School of Medical Sciences, Faculty of Medicine and Health, Örebro University, 702 81, Örebro, Sweden; Corresponding authors at: School of Medical Sciences, Örebro University, Örebro, Sweden.Environmental toxicants (ETs) are associated with adverse health outcomes. Here we hypothesized that exposures to ETs are linked with obesity and insulin resistance partly through a dysbiotic gut microbiota and changes in the serum levels of secondary bile acids (BAs). Serum BAs, per- and polyfluoroalkyl substances (PFAS) and additional twenty-seven ETs were measured by mass spectrometry in 264 Danes (121 men and 143 women, aged 56.6 ± 7.3 years, BMI 29.7 ± 6.0 kg/m2) using a combination of targeted and suspect screening approaches. Bacterial species were identified based on whole-genome shotgun sequencing (WGS) of DNA extracted from stool samples. Personalized genome-scale metabolic models (GEMs) of gut microbial communities were developed to elucidate regulation of BA pathways. Subsequently, we compared findings from the human study with metabolic implications of exposure to perfluorooctanoic acid (PFOA) in PPARα-humanized mice. Serum levels of twelve ETs were associated with obesity and insulin resistance. High chemical exposure was associated with increased abundance of several bacterial species (spp.) of genus (Anaerotruncus, Alistipes, Bacteroides, Bifidobacterium, Clostridium, Dorea, Eubacterium, Escherichia, Prevotella, Ruminococcus, Roseburia, Subdoligranulum, and Veillonella), particularly in men. Conversely, females in the higher exposure group, showed a decrease abundance of Prevotella copri. High concentrations of ETs were correlated with increased levels of secondary BAs including lithocholic acid (LCA), and decreased levels of ursodeoxycholic acid (UDCA). In silico causal inference analyses suggested that microbiome-derived secondary BAs may act as mediators between ETs and obesity or insulin resistance. Furthermore, these findings were substantiated by the outcome of the murine exposure study. Our combined epidemiological and mechanistic studies suggest that multiple ETs may play a role in the etiology of obesity and insulin resistance. These effects may arise from disruptions in the microbial biosynthesis of secondary BAs.http://www.sciencedirect.com/science/article/pii/S0160412024001557PFASGut microbiomeObesityInsulin resistanceSerum bile acids |
| spellingShingle | Partho Sen Yong Fan Jennifer J. Schlezinger Stanislav D. Ehrlich Thomas F. Webster Tuulia Hyötyläinen Oluf Pedersen Matej Orešič Exposure to environmental toxicants is associated with gut microbiome dysbiosis, insulin resistance and obesity Environment International PFAS Gut microbiome Obesity Insulin resistance Serum bile acids |
| title | Exposure to environmental toxicants is associated with gut microbiome dysbiosis, insulin resistance and obesity |
| title_full | Exposure to environmental toxicants is associated with gut microbiome dysbiosis, insulin resistance and obesity |
| title_fullStr | Exposure to environmental toxicants is associated with gut microbiome dysbiosis, insulin resistance and obesity |
| title_full_unstemmed | Exposure to environmental toxicants is associated with gut microbiome dysbiosis, insulin resistance and obesity |
| title_short | Exposure to environmental toxicants is associated with gut microbiome dysbiosis, insulin resistance and obesity |
| title_sort | exposure to environmental toxicants is associated with gut microbiome dysbiosis insulin resistance and obesity |
| topic | PFAS Gut microbiome Obesity Insulin resistance Serum bile acids |
| url | http://www.sciencedirect.com/science/article/pii/S0160412024001557 |
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