The Connection Between Leaky Gut and Arthritis

A healthy intestinal microbiome is essential to optimal wellness, and knowledge surrounding this relationship has grown substantially in recent years. The connection between gut health and rheumatoid arthritis (RA) development is one example, as the gut microbiota has been proposed to be an important environmental factor of the disease.¹ RA is one of several conditions where gut permeability predates symptoms, and it may be possible to prevent joint damage by treating the gut. What is the state of research on arthritis, the microbiome, and gut permeability? 

Inflammatory biomarkers are known to emerge years before a definitive diagnosis of rheumatoid arthritis is possible.² One theory dating back to the beginning of the 20^th century suggested that RA emerges from mucosal tissues and dysbiosis, and only later do problems occur in the synovial fluid and joints.^3,4 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.⁵ Studies continue to evaluate the relationship between RA risk and inflammatory indicators, including antibodies, cytokines, and proteins such as serum amyloid A (SAA).^6-8

People with RA have different gut microbial populations than people with other inflammatory diagnoses³—in particular, individuals newly diagnosed with RA have been found to have reduced levels of Faecalibacterium in the gut, a butyrate-generating beneficial bacterium.⁹ 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.¹⁰ 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.¹⁰

More recently, researchers in Japan performed a whole gut virome analysis based on the shotgun sequencing of 476 individuals with RA, systemic lupus erythematosus (SLE), multiple sclerosis (MS), and healthy controls.¹¹ The case-control comparison revealed that crAss-like phages, which are one of the main components of a healthy gut virome, significantly decreased in the gut of the patients with autoimmune diseases, specifically the patients with RA and SLE. Multiple bacterial targets of crAss-like phages were identified (e.g., Ruminococcus spp).¹¹ Higher levels of gingival disease and unhealthy oral microbiota are also associated with the early stage of RA.⁹ Taken together, these factors suggest that risk of RA development may be reduced for some patients if the signs are recognized early enough and gut health is restored.

In the following video, IFM educator Robert Rountree, MD, shares how he approaches arthritis and the importance of assessing the likely cause.

(Video Time: 2 minutes) Dr. Rountree has provided his unique combination of traditional family medicine, nutrition, herbology, and mind-body therapy in Boulder, CO, since 1983 and is a diplomate of the American Board of Holistic Medicine.

Influencing Outcomes

Another small but interesting September 2021 study, published in Genome Medicine, suggests that gut microbes and a patient’s outcome of RA may also be connected.¹² Researchers at the Mayo Clinic performed shotgun metagenomic sequencing on stool samples from 32 patients with RA at two separate clinical visits and compared the baseline gut microbiome compositions between RA patients who eventually showed improvement in disease activity and those who did not. They found several traits of the gut microbiome linked to future prognosis and used artificial intelligence to predict clinical outcomes with an accuracy of 90%. The results, write the authors, could implicate various aspects of the gut microbiome with improvement in chronic, debilitating symptoms in RA, raising the possibility of intervening on these markers, e.g., introducing specific desirable bacterial strains into the gut or targeting microbial metabolic pathways as a basis for therapeutic intervention.¹²

As research continues to suggest that gut dysbiosis may contribute to the development of some rheumatic diseases such as rheumatoid arthritis,¹³ what can you do for patients with intestinal permeability? 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. Romilly Hodges, MS, CNS, IFMCP, provides an overview of the many factors that increase and decrease gut permeability in an informative blog post¹⁴ published on the website of IFM educator Kara Fitzgerald, ND.

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) and how IFM tools such as the DIGIN model and 5R framework help to personalize gut health interventions.