The Role of Microbiome and Diet on Disease Activity and Immune Inflammatory Status in Rheumatoid Arthritis

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Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disease of autoimmune background and unknown etiology. The importance of genetic factors in the RA development is well established. Environmental factors have also been extensively researched in relation to risk of RA and managing its symptoms. Smoking, physical activity, diet and gut microbiota are considered to be the most essential modifiable factors in RA. Among dietary interventions the most researched is Mediterranean diet, monounsaturated fatty acids, fish consumption and fish oil (EPA, eicosapentaenoic acid and DHA, docosahexaenoic acid). Others concerned gluten-free and vegan or vegetarian diet, salt intake, supplementation with vitamin D, antioxidants, prebiotics and probiotics. Diet modifications can alter the gut environment and the association between RA development or severity and composition of gut bacteria has already been shown. This review focuses on effectiveness and usefulness of various dietary approaches and supplements in RA prevention and management, including influence on disease activity and inflammatory status. Composition of gut microbiota and its changes in response to dietary factors are also considered. There is a great need for further research into mutual dependencies of diet, microbiome and RA activity. The current state of knowledge provides promising evidence for future nutrition and microbial therapies.

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    Major Issues

    • Lack of experimental validation: The study remains largely correlative without in vivo or mechanistic experiments to support causal relationships between diet, microbiome alterations, and Rheumatoid Arthritis progression.

    • Absence of fasting-based models: No experiments were conducted to evaluate the impact of fasting on inflammatory markers or immune cell activity, despite its relevance in immune modulation.

    • No antibiotic perturbation experiments: The manuscript does not include microbiome depletion models (e.g., antibiotic-treated animals) to assess the direct role of gut microbiota in inflammation.

    • Missing dietary intervention studies: There is no controlled comparison of different dietary compositions (e.g., protein-, glucose-, or lipid-rich diets) and their effects on immune responses and inflammatory pathways.

    • Lack of rescue experiments: The study does not implement rescue approaches (e.g., microbiome restoration after severe inflammation) to demonstrate reversibility and strengthen causal inference.

    Minor Issues

    • Insufficient data visualization: The manuscript lacks clear and informative visualizations (e.g., microbiome composition plots, inflammatory marker trends), which limits clarity and data interpretation.

    • Limited methodological detail: Additional details on experimental design (or lack thereof) would improve transparency and reproducibility.

    Competing interests

    The author declares that they have no competing interests.

    Use of Artificial Intelligence (AI)

    The author declares that they did not use generative AI to come up with new ideas for their review.