Metabolites
Synovial SLC1A5-Associated Amino Acid Metabolic Features in Knee Osteoarthritis: An Integrated Analysis of Synovial Transcriptomics, Fecal Metabolomics, and Gut Microbiota
Par Xingzong Zhu, Hongrui Du, Bin Li et 2 autres.
Contenu en anglais
Résumé
Background
This exploratory study aimed to characterize amino acid related features in osteoarthritis (OA).
Methods
We analyzed independent public synovial transcriptomic datasets and paired fecal metabolomics and 16S ribosomal RNA profiles from 20 patients with knee OA and 14 controls. Metabolite-sensing genes were intersected with nominally differential genes and prioritized using elastic net, support vector machine recursive feature elimination, and extreme gradient boosting. Results:SLC1A5 (solute carrier family 1 member 5) expression was lower in the discovery cohort GSE89408 (log2 fold change = −0.532, p = 0.0159), but did not meet the false discovery rate (FDR) threshold of 0.05 (FDR = 0.0697). GSE55235 showed a concordant decrease (log2 fold change = −0.695, p = 0.00536; area under the receiver operating characteristic curve = 0.830). Single-cell computational predictions from three OA donors suggested endothelial, smooth muscle, and mast-cell contexts. Tissue-level SLC1A5 expression correlated with inferred M2 macrophage proportions after group adjustment (r = −0.575, FDR = 0.002). Six features with Level 3 putative glutamine-, asparagine-, or glutamate-containing tripeptide annotations differed between groups (q = 0.00245 to 0.00948), whereas the corresponding free amino acids did not reach FDR significance. Bacteroides showed a lower centered log-ratio value in OA (q = 0.00273); none of its six tripeptide correlations remained significant after group adjustment.