INVESTIGATING THE INTERPLAY BETWEEN GUT MICROBIOME, MONOCYTES/MACROPHAGES, AND OSTEOARTHRITIS

• Published in: Cytotherapy (Oxford, England) England), 2024-06, Vol.26 (6), p.S204-S204
• Main Authors: Ziyaeyan, A., Barazandeh, A. Feiz, rasti, M., Viswanathan, S.
• Format: Article
• Language: English
• Subjects: Gut dysbiosis; Monocytes/Macrophages; Osteoarthritis
• ISSN: 1465-3249; 1477-2566
• DOI: 10.1016/j.jcyt.2024.03.408

Osteoarthritis (OA) is a complex degenerative joint disease influenced by various factors, including gut dysbiosis. This research aims to unravel the complex connection between metabolites produced by intestinal commensal bacteria and their impact on local immune effectors within the joint. The synovial joint is not a sterile environment, as shown by elevated levels of bacterial metabolites, such as lipopolysaccharide (LPS), correlating with OA severity. We hypothesize that gut metabolites influence local and systemic immune effectors, specifically monocytes/macrophages (MΦ), contributing to OA pathogenesis. To test this hypothesis, we are measuring the correlation of levels of short-chain fatty acids (SCFAs) which are bacterial metabolites, LPS, LPS-binding protein (LBP) with i) patient-reported outcomes (PROMs) and ii) with frequencies of classical (CD14+CD16low), intermediate (CD14+CD16+) and non-classical (CD14lowCD16+) MΦ subsets. LBP levels are measured by an ELISA assay, and a Kinetic-QCL Kinetic Chromogenic LAL Assay measures LPS levels. The level of SCFAs is measured using liquid chromatography with tandem mass spectrometry (LC-MS/MS). The MΦ populations in the synovial fluid are investigated by flow cytometry. With an N=78, there was a significant negative correlation between the SF LBP and the frequency of intermediate and non-classical MΦ in SF, indicating that patients with higher levels of LBP in their SF had lower frequencies of intermediate and non-classical MΦ in their SF. In addition, there was a significant positive correlation between LBP levels in the plasma and intermediate MΦ, non-classical MΦ in SF, and the patient's body mass index (BMI). 34 out of 78 patients had BMIs ≥ 30 (considered obese). In these patients, we saw a positive correlation between LBP levels in SF and WOMAC-Function, showing that patients with higher LBP levels in their plasma were more functionally impaired. Of the 78 patients in our study, 43 were females, and 35 were males. There was a significant negative correlation between LBP levels in SF and SF intermediate MΦ frequency in males and females. In conclusion, the observed correlations in the patients suggest that gut metabolites, specifically LBP, have systemic effects on OA severity. Measuring the LPS and SCFA levels in serum and SF will allow us to get more information about this complex relationship.