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A healthy intestinal microbiome is essential to optimal wellness, and awareness of this relationship has grown substantially in recent years. One example of the surge in knowledge about the connection between gut and systemic health is rheumatoid arthritis (RA).
Inflammation, Microbial Makeup, and Permeability
Inflammatory biomarkers are known to emerge years before a definitive diagnosis of rheumatoid arthritis is possible.1,2 One theory dating back to the beginning of the 20th century suggested that RA emerges from mucosal tissues and dysbiosis, and only later do problems occur in the synovial fluid and joints.3-6 More recent research supports this chain of events.
For example, research suggests that IgA antibodies, which are closely associated with mucosa, are elevated in preclinical and recently diagnosed RA patients.7 People with RA have different gut microbial populations than people with other inflammatory diagnoses3—in particular, individuals newly diagnosed with RA have higher populations of Prevotella copri.8
A small 2019 study found significant differences in the microbial distribution of various taxa from phylum to genus levels between 25 healthy subjects and 29 early RA patients.9 Phylum Bacteroidetes was enriched in early RA patients, while Actinobacteria, including the genus Collinsella, was enriched in healthy subjects. Functional analysis based on clusters of orthologous groups revealed that the genes related to the biosynthesis of menaquinone, known to be derived from gram-positive bacteria, were enriched in healthy subjects, while iron transport–related genes were enriched in early RA patients. Genes related to the biosynthesis of lipopolysaccharide, the gram-negative bacterial endotoxin, were enriched in clinically apparent RA patients. Together, this research highlights the potential involvement of the gut microbiome even in the early stages of RA.9
Higher levels of gingival disease and unhealthy oral microbiota are also associated with the early stage of RA.10,11 Gut bacteria have also been found in the synovial fluid of RA mouse models, suggesting that treatment of mucosal surfaces and the microbiome may curtail or affect the development and course of RA.12 This suggests that RA might be avoidable if the signs are recognized early enough and gut health can be restored.13
In the following video, IFM educator Robert Rountree, MD, shares how he approaches arthritis and the importance of assessing the likely cause.
What can you do for patients with intestinal permeability? Romilly Hodges, MS, CNS, IFMCP, provides an overview of the many factors that increase and decrease gut permeability in an informative blog post published on the website of IFM educator Kara Fitzgerald, ND.14
Functional medicine helps clinicians understand the critical roles of gut mucosal integrity and microbial dysbiosis on patient health and provides key insights into preventing and treating chronic diseases related to gut dysfunction. Learn more about the interplay between the digestive system and the rest of the body at IFM’s Applying Functional Medicine in Clinical Practice (AFMCP).
- Karlson EW, Chibnik LB, Tworoger SS, et al. Biomarkers of inflammation and development of rheumatoid arthritis in women from two prospective cohort studies. Arthritis Rheum. 2009;60(3):641-652. doi:10.1002/art.24350
- Ramos-Remus C, Castillo-Ortiz JD, Aguilar-Lozano L, et al. Autoantibodies in prediction of the development of rheumatoid arthritis among healthy relatives of patients with the disease. Arthritis Rheumatol. 2015;67(11):2837-2844. doi:10.1002/art.39297
- Brusca SB, Abramson SB, Scher JU. Microbiome and mucosal inflammation as extra-articular triggers for rheumatoid arthritis and autoimmunity. Curr Opin Rheumatol. 2014;26(1):101-107. doi:10.1097/BOR.0000000000000008
- Yeoh N, Burton JP, Suppiah P, Reid G, Stebbings S. The role of the microbiome in rheumatic diseases. Curr Rheumatol Rep. 2013;15(3):314. doi:10.1007/s11926-012-0314-y
- Scherer HU, Häupl T, Burmester GR. The etiology of rheumatoid arthritis. J Autoimmun. 2020;110:102400. doi:10.1016/j.jaut.2019.102400
- Manasson J, Blank RB, Scher JU. The microbiome in rheumatology: where are we and where should we go? Ann Rheum Dis. 2020;79(6):727-733. doi:10.1136/annrheumdis-2019-216631
- Demoruelle MK, Deane KD, Holers VM. When and where does inflammation begin in rheumatoid arthritis? Curr Opin Rheumatol. 2014;26(1):64-71. doi:10.1097/BOR.0000000000000017
- Scher JU, Sczesnak A, Longman RS, et al. Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. Elife. 2013;2:e01202. doi:10.7554/eLife.01202
- Jeong Y, Kim JW, You HJ, et al. Gut microbial composition and function are altered in patients with early rheumatoid arthritis. J Clin Med. 2019;8(5):E693. doi:10.3390/jcm8050693
- Scher JU, Ubeda C, Equinda M, et al. Periodontal disease and the oral microbiota in new-onset rheumatoid arthritis. Arthritis Rheum. 2012;64(10):3083-3094. doi:10.1002/art.34539
- Chu XJ, Cao NW, Zhou HY, et al. The oral and gut microbiome in rheumatoid arthritis patients: a systematic review. Rheumatology (Oxford). 2021:60(3):1054-1066. doi:10.1093/rheumatology/keaa835
- Luckey D, Gomez A, Murray J, White B, Taneja V. Bugs & us: the role of the gut in autoimmunity. Indian J Med Res. 2013;138(5):732-743.
- Taneja V. Arthritis susceptibility and the gut microbiome. FEBS Lett. 2014;588(22):4244-4249. doi:10.1016/j.febslet.2014.05.034
- Hodges R, Kovalchik J, Herdell J. Expanding our view on leaky gut: beyond the ON/OFF idea. Dr. Kara Fitzgerald, Functional Medicine. Updated September 2020. Accessed March 2, 2021. http://www.drkarafitzgerald.com/2016/08/01/expanding-our-view-on-leaky-gut-beyond-the-onoff-idea/