Gut-joint axis: Gut dysbiosis can contribute to the onset of rheumatoid arthritis via multiple pathways

Abstract

Rheumatoid Arthritis (RA) is an autoimmune disease characterized by loss of immune tolerance and chronic inflammation. It is pathogenesis complex and includes interaction between genetic and environmental factors. Current evidence supports the hypothesis that gut dysbiosis may play the role of environmental triggers of arthritis in animals and humans. Progress in the understanding of the gut microbiome and RA. has been remarkable in the last decade. In vitro and in vivo experiments revealed that gut dysbiosis could shape the immune system and cause persistent immune inflammatory responses. Furthermore, gut dysbiosis could induce alterations in intestinal permeability, which have been found to predate arthritis onset. In contrast, metabolites derived from the intestinal microbiota have an immunomodulatory and anti-inflammatory effect. However, the precise underlying mechanisms by which gut dysbiosis induces the development of arthritis remain elusive. This review aimed to highlight the mechanisms by which gut dysbiosis could contribute to the pathogenesis of RA. The overall data showed that gut dysbiosis could contribute to RA pathogenesis by multiple pathways, including alterations in gut barrier function, molecular mimicry, gut dysbiosis influences the activation and the differentiation of innate and acquired immune cells, cross-talk between gut microbiota-derived metabolites and immune cells, and alterations in the microenvironment. The relative weight of each of these mechanisms in RA pathogenesis remains uncertain. Recent studies showed a substantial role for gut microbiota-derived metabolites pathway, especially butyrate, in the RA pathogenesis.

The gut-joint axis: Genetic evidence for a causal association between gut microbiota and seropositive rheumatoid arthritis and seronegative rheumatoid arthritis

“…The imbalance of GM may be involved in the pathogenesis of RA, but the mechanism of the gut-joint axis remains incompletely understood, which may be through the activation and differentiation of innate and acquired immune cells and sustained immune inflammatory response. [28] Given the different disease severity and outcome between seronegative and seropositive RA, we applied a two-sample MR approach to comprehensively explore the causal relationship between GM and RA subgroups (seropositive RA and seronegative RA). Our study found that Alloprevotella and Christensenellaceae R 7 group were negatively related to the risk of seropositive, and Ruminococcaceae UCG002 was positively associated with the seropositive RA risk.…”

Causal associations between gut microbiota and synovitis–tenosynovitis: a two-sample Mendelian randomization study

“…The interaction between gut microbiota and joint diseases is often described in terms of the “gut–joint axis” ( Zaiss et al, 2021 ). As part of the gut–joint axis, dysbiosis of gut microbiota can cause immune system disorders and a sustained immune inflammatory response, leading to the occurrence and development of synovitis and tenosynovitis ( Romero-Figueroa et al, 2023 ). To date, there has been accumulating evidence that the gut microbiota is involved in human joint diseases through multiple pathways ( Yang and Cong, 2021 ).…”

Border Control: The Role of the Microbiome in Regulating Epithelial Barrier Function

“…In addition to modifying immune functions, gut dysbiosis is hypothesised to contribute to RA pathology by disrupting the gut barrier function, which would facilitate the translocation of bacteria or their components/products into the lamina propria, spreading systemically and eventually leading to inflammatory responses [ 142 ]. Impaired barrier function has been reported in individuals with pre-clinical RA, early onset RA and fully established RA [ 112 , 143 ].…”