Fecal metabolomics reveals products of dysregulated proteolysis and altered microbial metabolism in obesity-related osteoarthritis.
Metabolomics
Microbiome
Obesity
Osteoarthritis
Proteolysis
Journal
Osteoarthritis and cartilage
ISSN: 1522-9653
Titre abrégé: Osteoarthritis Cartilage
Pays: England
ID NLM: 9305697
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
received:
28
05
2021
revised:
16
09
2021
accepted:
13
10
2021
pubmed:
1
11
2021
medline:
11
3
2022
entrez:
31
10
2021
Statut:
ppublish
Résumé
The 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). 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 16 S ribosomal RNA amplicon sequencing (rRNA-seq). Stepwise logistic regression models were built to determine microbiome and/or metabolic characteristics of OA. Untargeted 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. Adults 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.
Identifiants
pubmed: 34718137
pii: S1063-4584(21)00937-7
doi: 10.1016/j.joca.2021.10.006
pmc: PMC8712415
mid: NIHMS1752063
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
81-91Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK034987
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002489
Pays : United States
Organisme : NIDDK NIH HHS
ID : U24 DK097193
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK056350
Pays : United States
Organisme : NIAMS NIH HHS
ID : P30 AR072580
Pays : United States
Organisme : NIH HHS
ID : P40 OD010995
Pays : United States
Organisme : NCCDPHP CDC HHS
ID : U01 DP006266
Pays : United States
Informations de copyright
Copyright © 2021 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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