The Gut Microbiota in Osteoarthritis

Where Do We Stand and What Can We Do?

Xiaoxia Hao; Xingru Shang; Jiawei Liu; Ruimin Chi; Jiaming Zhang; Tao Xu


Arthritis Res Ther. 2021;23(42) 

In This Article

Concluding Remarks and Future Perspectives

OA represents a primary public health problem, which is a major source of pain, disability, and socioeconomic cost worldwide. Therefore, interpreting the potential mechanisms of OA pathogenesis is essential for developing novel prevention and disease-modifying therapeutic interventions.

In this narrative review, we summarized the evidence supporting the hypothesis of "gut-joint axis" and the interaction between gut microbiota and the OA-relevant factors and provided the reasonable speculations of the promising manipulation of gut microbiota in OA management. The evidence of the gut microbiota involvements upon the mechanisms of the risk factors, such as obesity and metabolic syndrome and joint injury, is more convincing compared to the others. Given that the intervention on gut microbiota to investigate its role in OA is scarce so far, the connections between gut microbiota and OA risk factors are still inconclusive. As a result, we call for the more convincing human longitudinal studies based on microbiota manipulation. Moreover, it is important to point out that this systematic low-degree inflammation induced by the disturbed gut microbiota is not specific for OA but rather favors the emergence of several potential diseases, such as metabolic syndrome and cardiovascular diseases. In this context, we speculate that the influence of gut microbiota on the OA subtypes may be different. Indeed, most of evidence is based on the Met-OA model, suggesting the potential interaction between gut microbiota, OA, and also other diseases. This adds another layer of complexity to the mechanisms of gut microbiota.

The detailed mechanisms of "gut-joint axis" remain reclusive. It is likely that gut microbiota influences joint by regulating inflammation and metabolism, while the gap between cartilage metabolism and gut microbiota still exists. In the context, multiple omics, such as metabonomic and transcriptomics, are helpful to link specific metabolites, genes, or signaling pathways contributing to the regulation of gut microbiota to decode this intricate matter in a molecular resolution. Also, single-cell technique is promising to reveal the relevance of distinct cell subgroups to gut microbiota. Besides the mechanism investigations, existing evidence also suggests the possibility of novel biomarkers related to inflammation and gut dysbiosis that are able to predict OA progression and monitor the efficacy of therapeutic intervention.