Gut Bacteria and Osteoarthritis
Full reference: Osteoarthritis treatment via the GLP-1–mediated gut-joint axis targets intestinal FXR signaling. Yang Y, Hao C, Jiao T, Yang Z, Li H, Zhang Y, Zhang W, Doherty M, Sun C, Yang T, Li J, Wu J, Zhang M, Wang Y, Xie D, Wang T, Wang N, Huang X, Li C, Gonzalez FJ, Wei J, Xie C, Zeng C, Lei G. Yuanheng Yang et al. Science 2025;388;48. doi.org/10.1126/science.adt0548.
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This study shows that reduced blood levels of bile acid salts produced by our gut bacteria influences development of osteoarthritis (OA). This presents a possible new avenue for treating OA.
There are millions of bacteria of different types living in our gut. Chemicals released from gut bacteria that are absorbed into the blood stream play an important role in maintaining our health. They do this by stabilising pathways involved in our metabolism (metabolism involves converting food into energy, building and repairing tissues, and eliminating waste products). However, an imbalance in gut bacteria and their products have been associated with certain diseases, for example, ulcerative colitis, diabetes and atherosclerosis. Recently, certain variations in the gut bacteria have also been associated with having OA, though the reason for this link has been unclear.
In this study, we first demonstrated in two different general population studies that people with knee OA have altered bacterial bile acid metabolism with low blood levels of various types of ursodeoxycholic acid (UDCA) compared to those without knee OA. People with knee OA also had less of the gut bacterium “Clostridium bolteae” which promotes production of UDCA. We next demonstrated that giving UDCA to mice reduced development of OA. We confirmed this result in humans in a large UK health record database study. In that study, we found that people taking UDCA for chronic liver problems were at lower risk of requiring total knee replacement due to OA than people not taking this medicine. Furthermore, in mice we found a positive correlation between blood levels of UDCA and glucagon-like peptide 1 (GLP-1), and a joint injection of GLP1 blocker abolished the positive effect of UDCA. Similarly, in a large health record database, regular use of GLP-1 medications for diabetes and weight management in humans reduced the risk of total knee replacement for OA. All this evidence strongly suggests that altering certain gut bacteria and the level of bacteria-related bile acids (UDCA) and the pathway they act through (GLP-1) may offer a new treatment approach for OA.