Summary of Study ST002496

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

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST002496
Study TitleStudy of environmental toxicants and gut microbiome in relation to obesity and insulin resistance
Study SummaryBackground & 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
DepartmentDepartment of Medical Sciences
LaboratorySystems Medicine
Last NameOrešič
First NameMatej
AddressSchool of Medical Sciences, Örebro, Örebro, 70281, Sweden
Emailmatej.oresic@oru.se
Phone+46 19 302137
Submit Date2023-02-21
Total Subjects264
Num Males121
Num Females143
Raw Data AvailableYes
Raw Data File Type(s)mzdata.xml
Analysis Type DetailLC-MS
Release Date2024-02-28
Release Version1
Matej Orešič Matej Orešič
https://dx.doi.org/10.21228/M8G12B
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

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)

Subject:

Subject ID:SU002655
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606
Gender:Not applicable

Factors:

Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id Factor
SA256586sample_0257none
SA256587sample_0165none
SA256588sample_0069none
SA256589sample_0077none
SA256590sample_0249none
SA256591sample_0056none
SA256592sample_0261none
SA256593sample_0264none
SA256594sample_0267none
SA256595sample_0202none
SA256596sample_0204none
SA256597sample_0247none
SA256598sample_0054none
SA256599sample_0148none
SA256600sample_0232none
SA256601sample_0233none
SA256602sample_0112none
SA256603sample_0126none
SA256604sample_0228none
SA256605sample_0103none
SA256606sample_0100none
SA256607sample_0087none
SA256608sample_0274none
SA256609sample_0214none
SA256610sample_0237none
SA256611sample_0099none
SA256612sample_0211none
SA256613sample_0164none
SA256614sample_0015none
SA256615sample_0186none
SA256616sample_0016none
SA256617sample_0275none
SA256618sample_0277none
SA256619sample_0011none
SA256620sample_0027none
SA256621sample_0191none
SA256622sample_0002none
SA256623sample_0006none
SA256624sample_0113none
SA256625sample_0081none
SA256626sample_0213none
SA256627sample_0114none
SA256628sample_0074none
SA256629sample_0252none
SA256630sample_0182none
SA256631sample_0072none
SA256632sample_0190none
SA256633sample_0145none
SA256634sample_0218none
SA256635sample_0008none
SA256636sample_0234none
SA256637sample_0106none
SA256638sample_0009none
SA256639sample_0196none
SA256640sample_0238none
SA256641sample_0137none
SA256642sample_0256none
SA256643sample_0132none
SA256644sample_0152none
SA256645sample_0058none
SA256646sample_0057none
SA256647sample_0053none
SA256648sample_0023none
SA256649sample_0028none
SA256650sample_0122none
SA256651sample_0172none
SA256652sample_0278none
SA256653sample_0044none
SA256654sample_0198none
SA256655sample_0266none
SA256656sample_0088none
SA256657sample_0143none
SA256658sample_0037none
SA256659sample_0108none
SA256660sample_0043none
SA256661sample_0082none
SA256662sample_0200none
SA256663sample_0055none
SA256664sample_0279none
SA256665sample_0038none
SA256666sample_0229none
SA256667sample_0139none
SA256668sample_0157none
SA256669sample_0167none
SA256670sample_0129none
SA256671sample_0134none
SA256672sample_0174none
SA256673sample_0177none
SA256674sample_0176none
SA256675sample_0201none
SA256676sample_0124none
SA256677sample_0123none
SA256678sample_0225none
SA256679sample_0189none
SA256680sample_0168none
SA256681sample_0197none
SA256682sample_0151none
SA256683sample_0184none
SA256684sample_0153none
SA256685sample_0209none
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Collection:

Collection ID:CO002648
Collection Summary:Fasting serum samples were collected for this study. None of the volunteers have undergone bariatric surgery or had taken antibiotics two months prior to their inclusion in the study. None of the participants were diagnosed with diabetes mellitus (Type 1 or 2). Thirty-four of study participants were taking statins at the time of study. The serum samples were stored at −80 °C until analyzed.
Sample Type:Blood (serum)
Storage Conditions:-80℃

Treatment:

Treatment ID:TR002667
Treatment Summary:Samples were stored at -80 as it is, and no treatment was done.

Sample Preparation:

Sampleprep ID:SP002661
Sampleprep Summary:40 µL of serum sample was mixed with 80 µL of acetonitrile including internal standards (TCA-d4, GUDCA-d4, GCA-d4, CA-d4, UDCA-d4, GCDCA-d4, CDCA-d4, DCA-d4, GLCA-d4 and LCA-d4; PFOA-13C8, PFNA-13C5, PFUndA-13C7, PFHxS-13C3 and PFOS-13C8, succinic acid-d4, glutamine-d5, valine-d8, tryptophan-d5, 3-hydroxybutyric acid-d4 and heptadecanoic acid-d5) and vortexed, ultrasonicated and centrifuged. 90 µL of the supernatant was evaporated to dryness and resuspended 60 µL of MeOH/H2O (70/30).
Processing Storage Conditions:-80℃
Extract Storage:-80℃

Combined analysis:

Analysis ID AN004206
Analysis type MS
Chromatography type Reversed phase
Chromatography system Agilent 1290 Infinity II
Column Waters ACQUITY UPLC BEH C18 (100 x 2.1mm,1.7um)
MS Type ESI
MS instrument type QTOF
MS instrument name Agilent 6545 QTOF
Ion Mode NEGATIVE
Units ng/ml

Chromatography:

Chromatography ID:CH003117
Instrument Name:Agilent 1290 Infinity II
Column Name:Waters ACQUITY UPLC BEH C18 (100 x 2.1mm,1.7um)
Column Temperature:50
Flow Gradient:from min 0-1.5, the percentage of phase B was increased from 5% to 30%, from min 1.5-4.5, the percentage of B was increased to 70%, from min 4.5-7.5 the percentage of B was increased to 100% and held for 5.5 mins. A post-time of 5 min was used to regain the initial conditions for the next analysis.
Flow Rate:0.4 mL/min
Solvent A:70% water/30% methanol; 2mM ammonium acetate
Solvent B:100% methanol; 2mM ammonium acetate
Chromatography Type:Reversed phase

MS:

MS ID:MS003953
Analysis ID:AN004206
Instrument Name:Agilent 6545 QTOF
Instrument Type:QTOF
MS Type:ESI
MS Comments:The analyses were done using UHPLC-QTOFMS instrument from Agilent Technologies (Santa Clara, CA, USA). The analysis was done on an ACQUITY UPLC® BEH C18 column (2.1 mm × 100 mm, particle size 1.7 µm) by Waters (Milford, MA, USA). Mobile phase A consisted of H2O:MeOH (v/v 70:30) and mobile phase B of MeOH with both phases containing 2mM ammonium acetate as an ionization agent. The LC pump was programmed at a flow rate of 0.4 mL/min with the elution gradient as follows: from min 0-1.5, the percentage of phase B was increased from 5% to 30%, from min 1.5-4.5, the percentage of B was increased to 70%, from min 4.5-7.5 the percentage of B was increased to 100% and held for 5.5 mins. A post-time of 5 min was used to regain the initial conditions for the next analysis. The total analysis time per sample was 18 min. The dual ESI ionization source was settings were as follows: capillary voltage was 4.5 kV, nozzle voltage 1500 V, N2 pressure in the nebulized was 21 psi and the N2 flow rate and temperature as sheath gas was 11 L/min and 379 °C, respectively. The m/z range 100-1700 in negative ion mode was used. MassHunter B.06.01 software (Agilent Technologies, Santa Clara, CA, USA) was used for all data acquisition. MS data processing was performed using open source software MZmine 2.5232. Quality control was performed throughout the dataset by including blanks, pure standard samples, and control plasma samples. The average RSD for the PFAS in QC samples was 10.6%, showing the robustness of the analytical procedure. The unknown compounds were identified based on exact mass and MS/MS data.
Ion Mode:NEGATIVE
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