The immune role of the intestinal microbiome in knee osteoarthritis: a review of the possible mechanisms and therapies

Abstract

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by cartilage damage and synovial inflammation and carries an enormous public health and economic burden. It is crucial to uncover the potential mechanisms of OA pathogenesis to develop new targets for OA treatment. In recent years, the pathogenic role of the gut microbiota in OA has been well recognized. Gut microbiota dysbiosis can break host-gut microbe equilibrium, trigger host immune responses and activate the “gut-joint axis”, which aggravates OA. However, although the role of the gut microbiota in OA is well known, the mechanisms modulating the interactions between the gut microbiota and host immunity remain unclear. This review summarizes research on the gut microbiota and the involved immune cells in OA and interprets the potential mechanisms for the interactions between the gut microbiota and host immune responses from four aspects: gut barrier, innate immunity, adaptive immunity and gut microbiota modulation. Future research should focus on the specific pathogen or the specific changes in the gut microbiota composition to identify the related signaling pathways involved in the pathogenesis of OA. In addition, future studies should include more novel interventions on immune cell modifications and gene regulation of specific gut microbiota related to OA to validate the application of gut microbiota modulation in the onset of OA.

Bioactives and their roles in bone metabolism of osteoarthritis: evidence and mechanisms on gut-bone axis

“…Although the functions of bioactive compounds influencing osteoarthritis pathophysiology are reported, their modulation of the intestinal microbiome via the gut-bone axis is not known. In addition, there is paramount evidence that gut microbiota modulates host immune responses in osteoarthritis; however, the exact mechanisms are still unknown ( 11 ). In that context, this narrative review highlights recent mechanistic evidence on using bioactive or functional foods to ameliorate osteoarthritis and inflammatory diseases.…”

Exploratory analysis on the relationship between dietary live microbe intake and arthritis: a national population based cross-sectional study

“…Some studies have also shown that intestinal microbes and their related components and metabolites may be involved in the pathogenesis of OA by activating local or systemic innate immune responses. However, the precise mechanism behind this association remains unclear ( 11 , 12 ). Compared with tumors, metabolic diseases and nervous system diseases, the distribution and changes of intestinal microbes in autoimmune diseases are more consistent, which is of great significance for the prediction of autoimmune diseases ( 13 ).…”

Association of Life's Essential 8 with osteoarthritis in United States adults: mediating effects of dietary intake of live microbes

“…Beneficial symbiotic microbes have also been found to be capable of exerting cholesterol-lowering effects ( 14 ). In addition, studies have reported that gut dysbiosis exacerbates OA; this may be explained by disruption of the host–gut microbial balance, which, in turn, triggers the host immune response and activates the “gut–joint axis” ( 15 ). Research suggests that LE8 scores and live microbe intake may reduce the risk of OA by reducing oxidative stress, inflammation, and obesity ( 16 ).…”