The role of gut flora-driven Th cell responses in preclinical rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder with an immune pathogenesis that evolves over decades. Preclinical RA (PreRA) represents a dynamic immune phase preceding clinical RA, marked by the loss of autoimmune tolerance, the appearance of tissue-invasive effector T cells, and the production of autoantibodies (such as antibodies against citrullinated proteins and rheumatoid factors). Extensive research has demonstrated that gut microbiota influence mucosal T-cell responses, driving the progression of PreRA through multiple mechanisms, including altered intestinal permeability, gene-environment interactions, bacterial antigenic specificity, molecular mimicry, and metabolite production. Environmental risk factors such as smoking, hormonal changes, and high-sodium (Na) diets, may contribute to RA pathogenesis via the gut microbiome. The next challenge in RA research lies in developing therapeutic strategies to intervene during the asymptomatic autoimmune phase, where dietary adjustments, natural compounds, probiotics, and other approaches could effectively modulate gut flora to prevent or delay RA onset.