Evidence mapPaperPMID 34718137Full record

ArticleOsteoarthritis and cartilage2022

Fecal metabolomics reveals products of dysregulated proteolysis and altered microbial metabolism in obesity-related osteoarthritis.

B R Rushing, S McRitchie, L Arbeeva, A E Nelson, M A Azcarate-Peril, Y-Y Li, Y Qian, W Pathmasiri, S C J Sumner, R F Loeser

Open access · greenAbstract read
In one paragraph

Article in Osteoarthritis and cartilage, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 1 pooled it
2.8field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

36 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. The gut-joint axis in osteoarthritis.Nature reviews. Rheumatology · 2026
    Review
  5. Article
  6. Review
  7. Review
  8. Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Review
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

B R RushingDepartment of Nutrition, University of North Carolina at Chapel Hill, Nutrition Research Institute, Kannapolis, NC, USA.
S McRitchieDepartment of Nutrition, University of North Carolina at Chapel Hill, Nutrition Research Institute, Kannapolis, NC, USA.
L ArbeevaDepartment of Medicine, Division of Rheumatology, Allergy and Immunology and the Thurston Arthritis Research Center, University of North Carolina, Chapel Hill, NC, USA.
A E NelsonDepartment of Medicine, Division of Rheumatology, Allergy and Immunology and the Thurston Arthritis Research Center, University of North Carolina, Chapel Hill, NC, USA.
M A Azcarate-PerilDepartment of Medicine, Division of Gastroenterology and Hepatology and UNC Microbiome Core, Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA.
Y-Y LiDepartment of Nutrition, University of North Carolina at Chapel Hill, Nutrition Research Institute, Kannapolis, NC, USA.
Y QianDepartment of Nutrition, University of North Carolina at Chapel Hill, Nutrition Research Institute, Kannapolis, NC, USA.
W PathmasiriDepartment of Nutrition, University of North Carolina at Chapel Hill, Nutrition Research Institute, Kannapolis, NC, USA.
S C J SumnerDepartment of Nutrition, University of North Carolina at Chapel Hill, Nutrition Research Institute, Kannapolis, NC, USA. Electronic address: susan_sumner@unc.edu.
R F LoeserDepartment of Medicine, Division of Rheumatology, Allergy and Immunology and the Thurston Arthritis Research Center, University of North Carolina, Chapel Hill, NC, USA. Electronic address: richard_loeser@med.unc.edu.
David H. Murdock Research Institute · USUniversity of North Carolina at Chapel Hill · USUniversity of North Carolina Health Care · US

Funding

PILOT AND FEASIBILITY STUDIESP30DK034987 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · 1985 to 2025
$14.1M
UNIV OF NORTH CAROLINA CLINICAL NUTRITION RESEARCH UNITP30DK056350 · UNIV OF NORTH CAROLINA CHAPEL HILL · 1999 to 2025
$5.9M
National Gnotobiotic Resource CenterP40OD010995 · UNIV OF NORTH CAROLINA CHAPEL HILL · 2025 to 2025
$776k
UNC Core Center for Clinical ResearchP30AR072580 · UNIV OF NORTH CAROLINA CHAPEL HILL · 2025 to 2025
$633k
ACL HHS U01DP006266NCATS NIH HHS UL1 TR002489NCCDPHP CDC HHS U01 DP006266NIAMS NIH HHS P30 AR072580NIDDK NIH HHS P30 DK034987NIDDK NIH HHS P30 DK056350NIDDK NIH HHS U24 DK097193NIH HHS P40 OD010995
6 · The paper itself

Abstract

objectiveThe objective of this exploratory study was to determine if perturbations in gut microbial composition and the gut metabolome could be linked to individuals with obesity and osteoarthritis (OA).

methodsFecal 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 16 S ribosomal RNA amplicon sequencing (rRNA-seq). Stepwise logistic regression models were built to determine microbiome and/or metabolic characteristics of OA.

resultsUntargeted metabolomics analysis indicated that OA cases had significantly higher levels of di- and tripeptides 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.

conclusionsAdults with obesity and knee plus hand 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.

Indexed as

MetabolomeProteolysisAgedFecesFemaleHumansMaleObesityOsteoarthritisMetabolomicsMicrobiomeObesityOsteoarthritisProteolysis

Identifiers

PMID34718137
PMCPMC8712415
OpenAlexW3210660659

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.