Summary of project PR001611
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001611. The data can be accessed directly via it's Project DOI: 10.21228/M8G12B This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001611 |
| Project DOI: | doi: 10.21228/M8G12B |
| Project Title: | Study of environmental toxicants and gut microbiome in relation to obesity and insulin resistance |
| Project Summary: | Background & Aims: Environmental toxicants (ETs) associate with various adverse health outcomes. Here, we hypothesized that exposures to ETs are associated with obesity and insulin resistance via a dysbiotic gut microbiota and derived alterations in microbiome-mediated bile acid (BA) synthesis. Methods: Serum BAs, per- and polyfluoroalkyl substances (PFAS) and additional twenty-seven ETs were measured by mass spectrometry in 264 Danes (121 women and 143 men, age 56.6 ± 7.3 years, BMI 29.7 ± 6.0 kg/m2). Bacterial species were identified based on whole-genome shotgun (WGS) sequencing of DNA extracted from purified stool samples. Personalized genome-scale metabolic models (GEMs) of gut microbial communities were developed to elucidate regulation of BA pathways. Subsequently, we compared findings in the human study with metabolic implications of perfluorooctanoic acid (PFOA) exposure in a PPAR?-humanized murine model. Results: Fasting serum concentrations of twelve ETs associated directly with measures of obesity and insulin resistance. Several bacterial species including Dorea longicatena, Dorea formicigenerans, Subdoligranulum spp., Veillonella spp., and Roseburia intestinalis associated positively and in a sex-dimorphic manner, particularly in women, with high exposure to ETs. Moreover, high serum concentrations of ETs were linked with higher fasting serum levels of microbiome-synthesized secondary BAs such as lithocholic acid (LCA) and ursodeoxycholic acid (UDCA). These findings were substantiated by the outcome of a murine exposure study. Conclusion: Serum concentrations of ETs, particularly in women, were associated with an altered gut microbiome-mediated secondary BA biosynthesis, linked with obesity and insulin resistance. |
| Institute: | Örebro University |
| Department: | Department of Medical Sciences |
| Laboratory: | Systems Medicine |
| Last Name: | Orešič |
| First Name: | Matej |
| Address: | School of Medical Sciences, Örebro, Örebro, 70281, Sweden |
| Email: | matej.oresic@oru.se |
| Phone: | +46 19 302137 |
| Funding Source: | Academy of Finland (grant no. 333981 to M.O.), Novo Nordisk Foundation (grants no. NNF20OC0063971 and NNF21OC0070309 to T.H.), Swedish Research Council (grant no. and 2020-03674 to T.H and M.O), Formas (grant no. 2019-00869 to T.H and M.O). |
| Contributors: | Matej Orešič (M.O) and Tuulia Hyötyläinen (T.H) |
Summary of all studies in project PR001611
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002496 | Study of environmental toxicants and gut microbiome in relation to obesity and insulin resistance | Homo sapiens | Örebro University | MS | 2024-02-28 | 1 | 264 | Uploaded data (714M)* |
