1. Villafane, Jorge Hugo PhD

Article Content

Osteoarthritis (OA) is not simply a matter of mechanical damage, and in the past 20 years, it has become clear that several risk factors are involved in the manifestation of the OA phenotype. Abnormal joint biomechanics, age, gender, injuries, obesity, genetic, stress, and psychological factors are related to the presence of OA symptoms; however, there is still a discrepancy between pain and structural damage.1 OA results in chronic pain, and symptoms are confounded by other factors affecting the central processing of pain (ie, anxiety, depression, and increased pain sensitivity).2 Sensitization is a significant contributor to pain in OA, and a high degree of general sensitization in OA is related to3 high level of pain, disability, and decreased quality of life.


The involvement of the gut microbiota has been proven to be of crucial importance in the development of several metabolic and inflammatory diseases.4 The exact role of the gut microbiota in the pathophysiology of OA remains under investigation.5 For instance, the translocation of bacteria or related compounds (ie, lipopolysaccharides) across the gut barrier into the systemic circulation was found to mediate OA.4 Exposure to stress and pain may lead to alteration in brain-gut interactions (the brain-gut axis) by changing gastrointestinal secretion and intestinal permeability, thus contributing to dysbiosis and increasing the rate of translocation of intestinal bacterial and inflammatory products.6 The gut microbiota profile changes with aging, diet, and lifestyle, and the loss of microbiota diversity and alterations in the "optimal," healthy configuration, with depletion of beneficial microbes and enrichment in pathobionts, are believed to increase the risk of many diseases.7 OA is now considered an induced inflammatory condition where the role of the microbiome is emerging as an important factor. Several publications discuss the possibility of a link between OA and gut microbiota dysbiosis.4,8,9


In the last decades, the burden of OA increased not only because of longer life expectancy but also because of the modern lifestyle, in particular physical inactivity and improper diets, which promote chronic low-grade inflammation and obesity.10 The prevalence of OA and the need to define preventive and therapeutic interventions targeting the modifiable components of OA led researchers to develop new methods of managing the disease. There is currently no gold standard method with which to treat patients with OA. OA management is considered a multimodal process involving education, lifestyle advice, exercise, and dietary therapy. Conservative nonpharmacological treatment has shown to relieve symptoms in patients with early stage of OA disease and can stave off surgical interventions either temporarily or in the long term. Applying a multimodal treatment that includes targeting the gut microbiota is a relatively new therapeutic technique that can be easily applied by physicians in different clinical settings in the National Health Service worldwide. Our hypothesis opens ways for future research in the modulation of pain pathways, perhaps offering targets to optimize pain management in OA. Understanding the associations between OA and gut microbiota can lead to improved treatment approaches, focusing on the most efficient therapies.


-Jorge Hugo Villafane, PhD


Issue Editor




1. Glyn-Jones S, Palmer AJ, Agricola R, et al Osteoarthritis. Lancet.2015;386(9991):376-387. [Context Link]


2. Villafane JH, Valdes K, Pedersini P, Berjano P. Osteoarthritis: a call for research on central pain mechanism and personalized prevention strategies. Clin Rheumatol.2019;38(2):583-584. [Context Link]


3. Villafane JH, Cleland JA, Fernandez-de-Las-Penas C. Bilateral sensory effects of unilateral passive accessory mobilization in patients with thumb carpometacarpal osteoarthritis. J Manipulative Physiol Ther.2013;36(4):232-237. [Context Link]


4. Huang ZY, Stabler T, Pei FX, Kraus VB. Both systemic and local lipopolysaccharide (LPS) burden are associated with knee OA severity and inflammation. Osteoarthritis Cartilage.2016;24(10):1769-1775. [Context Link]


5. Drago L, Zuccotti GV, Romano CL, et al Oral-gut microbiota and arthritis: is there an evidence-based axis? J Clin Med.2019;8(10). doi:10.3390/jcm8101753. [Context Link]


6. Mukhtar K, Nawaz H, Abid S. Functional gastrointestinal disorders and gut-brain axis: what does the future hold? World J Gastroenterol.2019;25(5):552-566. [Context Link]


7. Villafane JH, Drago L. What is the site of pain osteoarthritis? A triple gut-brain-joint microbioma axis. Clin Exp Rheumatol.2019;37(6)(suppl 122):20-21. [Context Link]


8. Collins KH, Paul HA, Reimer RA, Seerattan RA, Hart DA, Herzog W. Relationship between inflammation, the gut microbiota, and metabolic osteoarthritis development: studies in a rat model. Osteoarthritis Cartilage.2015;23(11):1989-1998. [Context Link]


9. Sanchez-Romero EA, Melendez E, Alonso-Perez JL, et al Relationship between the gut microbiome and osteoarthritis pain: review of the literature. Nutrients. 2021;13(3):716. [Context Link]


10. Villafane JH, Bishop MD, Pedersini P, Berjano P. Physical activity and osteoarthritis: update and perspectives. Pain Med.2019;20(8):1461-1463. [Context Link]