The role of the microbiome in rheumatoid arthritis: a review

• Published in: Rheumatology advances in practice Vol. 7; no. 2; p. rkad034
• Main Authors: Tsetseri, Maria-Nefeli, Silman, Alan J, Keene, David J, Dakin, Stephanie G
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 2023
• Subjects: Arthritis; B cells; Immune response; Inflammation; Medical research; Medicine, Experimental; Microbiota (Symbiotic organisms); Review; Rheumatoid factor; intestinal; pathogenesis; microbiome; RA; dysbiosis
• ISSN: 2514-1775; 2514-1775
• DOI: 10.1093/rap/rkad034

Abstract The close bidirectional relationship between the microbiome and the immune system is well supported, and a role of gut dysbiosis has been implied in many systemic autoimmune diseases. This review aims to provide a critical summary and appraisal of 6 murine studies and 16 clinical studies. The findings of the literature review suggest that gut dysbiosis precedes arthritis and that local intestinal inflammation leads to systemic inflammation in genetically predisposed individuals. However, the exact mechanism by which microorganisms provoke immune responses at distal sites remains to be elucidated. Although a characteristic RA microbiome was not identified, there were some common findings among studies: overabundance of Prevotella copri in early RA patients, and proliferation of the genus Collinsela and some Lactobacillus species. Three mechanisms by which microbiota might contribute to RA pathogenesis were proposed: inflammatory responses (P. copri and Lactobacillus), molecular mimicry (P. copri) and loss of intestinal barrier integrity (Collinsella). Larger longitudinal studies are required in order to shed light on the mechanisms involved and unravel the therapeutic potential of the microbiome, and clinical trials are needed to evaluate the safety and efficacy of the implied therapeutic interventions. Lay Summary What does this mean for patients? The human body harbours a huge and diverse population of small organisms collectively called the microbiome, mainly residing in the gut. The microbiome differs among individuals, but also within the same individual over time, for various reasons, including diet and the use of antibiotics. The small organisms living in our bodies are essential for our health because they play an important role for digestion and protection. Studies in mice and humans have shown that the microbiome and the immune system, the body’s protective system, influence and determine each other. It is therefore not surprising that it has been hypothesized that disruptions in the microbiome might be linked to diseases of the immune system. Recent technological advancements are establishing the specific role of the microbiome in RA. RA is an autoimmune disease in which the immune system attacks healthy cells, which affects the whole body but is characterized mainly by joint pain and inflammation. Although alterations in the microbiome are well reported in RA patients, it remains unclear which organisms (present or absent) contribute (and how) to the development of RA. This review looks at studies in both mice and humans aiming to reveal the role of the microbiome in the development of RA. It is concluded that studies in mice show that changes in the microbiome activate immune cells locally, which then enter the body circulation and migrate to joints, causing distraction. The results of studies in humans are extensive, complex and not consistent. However, all studies demonstrate alterations in the microbiome of RA patients, implying that the microbiome plays a central role in RA. These are important findings because they imply the therapeutic value of minimally invasive treatments, such as diet and supplementation.