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.
| Study ID | ST001914 |
| Study Title | Fecal Metabolomics Reveals Products of Dysregulated Proteolysis and Altered Microbial Metabolism in Obesity-Related Osteoarthritis |
| Study Type | C18 Untargeted UPLC-MS Metabolomics Analysis |
| Study 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 | Nutrition |
| Laboratory | Metabolomics and Exposome Laboratory, Nutrition Research Institute, UNC Chapel Hill |
| Last Name | Susan |
| First Name | Sumner |
| Address | 500 Laureate Way, Kannapolis, NC 28081 |
| susan_sumner@unc.edu | |
| Phone | 9196224456 |
| Submit Date | 2021-09-08 |
| Num Groups | 2 (excluding QC group) |
| Total Subjects | 92 |
| Num Males | 69 |
| Num Females | 23 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2022-09-14 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
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 |
