Summary of Study ST001914

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 PR001207. The data can be accessed directly via it's Project DOI: 10.21228/M8PQ6M 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 IDST001914
Study TitleFecal Metabolomics Reveals Products of Dysregulated Proteolysis and Altered Microbial Metabolism in Obesity-Related Osteoarthritis
Study TypeC18 Untargeted UPLC-MS Metabolomics Analysis
Study SummaryObjective. The objective of this study was to determine if perturbations in gut microbial composition and the gut metabolome could be linked to individuals with obesity and osteoarthritis (OA). Methods. Fecal samples were collected from obese individuals diagnosed with radiographic hand plus knee OA (n=59), defined as involvement of at least 3 joints across both hands, and a Kellgren-Lawrence (KL) grade 2-4 (or total knee replacement) in at least one knee. Controls (n=33) were without hand OA and with KL grade 0-1 knees. Fecal metabolomes were analyzed by a UHPLC/Q Exactive HFx mass spectrometer. Microbiome composition was determined in fecal samples by 16S ribosomal RNA amplicon sequencing (rRNA-seq). Stepwise logistic regression models were built to determine microbiome and/or metabolic characteristics of OA. Results. Untargeted metabolomics analysis indicated that OA cases had significantly higher levels of di- and tri-peptides and significant perturbations in microbial metabolites including propionic acid, indoles and other tryptophan metabolites. Pathway analysis revealed several significantly perturbed pathways associated with OA including leukotriene metabolism, amino acid metabolism and fatty acid utilization. Logistic regression models selected metabolites associated with the gut microbiota and leaky gut syndrome as significant predictors of OA status, particularly when combined with the rRNA-seq data. Conclusions. Adults with obesity and OA have distinct fecal metabolomes characterized by increased products of proteolysis, perturbations in leukotriene metabolism, and changes in microbial metabolites compared with controls. These metabolic perturbations indicate a possible role of dysregulated proteolysis in OA.
Institute
University of North Carolina at Chapel Hill
DepartmentNutrition
LaboratoryMetabolomics and Exposome Laboratory, Nutrition Research Institute, UNC Chapel Hill
Last NameSusan
First NameSumner
Address500 Laureate Way, Kannapolis, NC 28081
Emailsusan_sumner@unc.edu
Phone9196224456
Submit Date2021-09-08
Num Groups2 (excluding QC group)
Total Subjects92
Num Males69
Num Females23
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2022-09-14
Release Version1
Sumner Susan Sumner Susan
https://dx.doi.org/10.21228/M8PQ6M
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR001207
Project DOI:doi: 10.21228/M8PQ6M
Project Title:Fecal Metabolomics Reveals Products of Dysregulated Proteolysis and Altered Microbial Metabolism in Obesity-Related Osteoarthritis
Project Type:C18 Reversed-Phase Broad Spectrum Metabolomics
Project Summary:Objective. The objective of this study was to determine if perturbations in gut microbial composition and the gut metabolome could be linked to individuals with obesity and osteoarthritis (OA). Methods. Fecal samples were collected from obese individuals diagnosed with radiographic hand plus knee OA (n=59), defined as involvement of at least 3 joints across both hands, and a Kellgren-Lawrence (KL) grade 2-4 (or total knee replacement) in at least one knee. Controls (n=33) were without hand OA and with KL grade 0-1 knees. Fecal metabolomes were analyzed by a UHPLC/Q Exactive HFx mass spectrometer. Microbiome composition was determined in fecal samples by 16S ribosomal RNA amplicon sequencing (rRNA-seq). Stepwise logistic regression models were built to determine microbiome and/or metabolic characteristics of OA. Results. Untargeted metabolomics analysis indicated that OA cases had significantly higher levels of di- and tri-peptides and significant perturbations in microbial metabolites including propionic acid, indoles and other tryptophan metabolites. Pathway analysis revealed several significantly perturbed pathways associated with OA including leukotriene metabolism, amino acid metabolism and fatty acid utilization. Logistic regression models selected metabolites associated with the gut microbiota and leaky gut syndrome as significant predictors of OA status, particularly when combined with the rRNA-seq data. Conclusions. Adults with obesity and OA have distinct fecal metabolomes characterized by increased products of proteolysis, perturbations in leukotriene metabolism, and changes in microbial metabolites compared with controls. These metabolic perturbations indicate a possible role of dysregulated proteolysis in OA.
Institute:University of North Carolina at Chapel Hill
Department:Medicine
Laboratory:UNC Thurston Arthritis Research Center, Division of Rheumatology, Allergy & Immunology
Last Name:Loeser
First Name:Richard
Address:3300 Thurston Building Campus Box 7280 Chapel Hill, NC 27599-7280
Email:richard_loeser@med.unc.edu
Phone:866-827-2862

Subject:

Subject ID:SU001992
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606
Gender:Male and female
Species Group:Mammals

Factors:

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

mb_sample_id local_sample_id group gender
SA177602F_47case F
SA177603F_45case F
SA177604F_48case F
SA177605F_49case F
SA177606F_51case F
SA177607F_44case F
SA177608F_40case F
SA177609F_36case F
SA177610F_35case F
SA177611F_37case F
SA177612F_38case F
SA177613F_53case F
SA177614F_43case F
SA177615F_54case F
SA177616F_74case F
SA177617F_72case F
SA177618F_8case F
SA177619F_84case F
SA177620F_90case F
SA177621F_65case F
SA177622F_64case F
SA177623F_56case F
SA177624F_58case F
SA177625F_61case F
SA177626F_62case F
SA177627F_34case F
SA177628F_55case F
SA177629F_20case F
SA177630F_21case F
SA177631F_22case F
SA177632F_12case F
SA177633F_13case F
SA177634F_19case F
SA177635F_33case F
SA177636F_16case F
SA177637F_18case F
SA177638F_26case F
SA177639F_23case F
SA177640F_29case F
SA177641F_30case F
SA177642F_31case F
SA177643F_32case F
SA177644F_28case F
SA177645F_59case M
SA177646F_39case M
SA177647F_63case M
SA177648F_41case M
SA177649F_57case M
SA177650F_46case M
SA177651F_24case M
SA177652F_76control F
SA177653F_86control F
SA177654F_73control F
SA177655F_15control F
SA177656F_85control F
SA177657F_14control F
SA177658F_71control F
SA177659F_89control F
SA177660F_91control F
SA177661F_80control F
SA177662F_92control F
SA177663F_82control F
SA177664F_78control F
SA177665F_79control F
SA177666F_11control F
SA177667F_68control F
SA177668F_1control F
SA177669F_6control F
SA177670F_52control F
SA177671F_3control F
SA177672F_4control F
SA177673F_60control F
SA177674F_25control F
SA177675F_67control F
SA177676F_69control F
SA177677F_17control F
SA177678F_9control M
SA177679F_88control M
SA177680F_77control M
SA177681F_42control M
SA177682F_7control M
SA177683F_87control M
SA177684F_10control M
SA177685F_27control M
SA177686F_2control M
SA177687F_75control M
SA177688F_70control M
SA177689F_81control M
SA177690F_66control M
SA177691F_50control M
SA177692F_5control M
SA177693F_83control M
SA177694SP_7quality control pool -
SA177695SP_8quality control pool -
SA177696SP_9quality control pool -
SA177697SP_6quality control pool -
SA177698SP_2quality control pool -
SA177699SP_1quality control pool -
SA177700SP_3quality control pool -
SA177701SP_4quality control pool -
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Collection:

Collection ID:CO001985
Collection Summary:Fecal samples were collected at each participant's home in and placed in a plastic biohazard bag with a frozen icepack to keep the samples cold. The samples were picked up by study personnel or returned to the study clinic by the participant within 24 hours of the time the stool was collected. Stool samples were stored at the clinic site in a -200C freezer for up to one week until transfer to a -800C freezer where samples were kept until processing.
Sample Type:Feces
Storage Conditions:-80℃

Treatment:

Treatment ID:TR002004
Treatment Summary:NA

Sample Preparation:

Sampleprep ID:SP001998
Sampleprep Summary:Ninety-two fecal samples (250-300 mg) were randomized and homogenized in 50:50 acetonitrile:water (5 mL/ mg fecal mass) in MagNALyser tubes with ceramic beads, using an Omni Bead Ruptor (5 meters per second, two 30-sec cycles, 15 sec dwell time in between cycles). Samples were centrifuged at 16,000 relative centrifugal force (rcf) for 15 min, the supernatant was transferred, and centrifuged again at 16,000 rcf for 5 min. Quality control (QC) samples were prepared by pooling 70 µL supernatant from each of the study samples and processed identically to the study samples. An aliquot of the supernatant (100 mL) from each sample was transferred to 2.0 mL tubes and dried overnight by SpeedVac and then reconstituted in 200 mL of reconstitution solution (95:5 water-methanol solvent containing 500 ng/ml tryptophan d-5). Samples were centrifuged at 16,000 rcf at 4°C for 4 minutes and the supernatants were transferred to autosampler vials. The study samples were randomized with interspersed QC pools before data acquisition. An injection volume of 5 mL was used for the UPLC-MS analysis.
Sampleprep Protocol Filename:OA-Fecal LCMS procedures
Processing Method:Extraction
Processing Storage Conditions:On ice
Extract Storage:-80℃
Sample Resuspension:95:5 water-methanol solvent containing 500 ng/ml tryptophan d-5

Combined analysis:

Analysis ID AN003112
Analysis type MS
Chromatography type Unspecified
Chromatography system none
Column none
MS Type ESI
MS instrument type Orbitrap
MS instrument name Orbitrap Q-Exactive HF-X
Ion Mode POSITIVE
Units Normalized intensity

Chromatography:

Chromatography ID:CH002297
Instrument Name:none
Column Name:none
Column Pressure:6000-10000
Column Temperature:50
Flow Gradient:Time(min) Flow Rate %A %B Curve 1. 0 0.4 99.0 1.0 5 2. 1.00 0.4 99.0 1.0 5 3. 16.00 0.4 1.0 99.0 5 4. 19.00 0.4 1.0 99.0 5 5. 19.50 0.4 99.0 1.0 5
Flow Rate:0.4 mL/min
Injection Temperature:8
Internal Standard:Tryptophan-d5
Solvent A:100% water; 0.1% formic acid
Solvent B:100% methanol; 0.1% formic acid
Analytical Time:22 min
Weak Wash Solvent Name:10:90 Methanol:Water with 0.1% FA solution
Strong Wash Solvent Name:75:25 2-Propanol: Water with 0.1% FA solution
Randomization Order:Yes
Chromatography Type:Unspecified

MS:

MS ID:MS002893
Analysis ID:AN003112
Instrument Name:Orbitrap Q-Exactive HF-X
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:We used DDA mode to acquire the MS and MS/MS data. Progenesis QI was used for peak picking, alignment, and normalization.
Ion Mode:POSITIVE
Capillary Temperature:275 °C
Capillary Voltage:3.5 KV
Collision Energy:10-35, ramp
Collision Gas:N2
Dry Gas Flow:45
Dry Gas Temp:325°C
Fragmentation Method:CID
Mass Accuracy:5 ppm
Desolvation Gas Flow:45
Desolvation Temperature:325°C
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