- Sep 21, 2023
- 4 min read

RA and Gut Health - What does the latest science say?

Updated: Sep 22, 2023

I recently did a presentation on this topic on my YouTube Channel. You can watch the full video here:

For a while now it has been well-known in the functional medicine world that a 'leaky gut' is what triggers autoimmune disease. My blog post on gut health explains in detail how poor digestion as well as lifestyle and environmental factors can cause our gut to become leaky.

Leaky Gut and autoimmunity:

Dr Sarah Ballantyne, Ph.D, author of the book, 'The Paleo Approach', says in her book that 'Leaky gut is present in every autoimmune disease that has been tested: rheumatoid arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, celiac disease, multiple sclerosis, and type 1 diabetes and is a pre-requisite for autoimmunity to develop' (1). When the lining of our intestine becomes ‘leaky’, it triggers our immune system leading to food sensitivities and subsequently inflammation. This happens due to the close working of our immune system with our digestive system. Yes, 80% of your immune system is located in your gut!

Now the latest research shows that RA is one of several conditions where gut permeability predates symptoms, and it may be possible to prevent joint damage by treating the gut (2). Inflammatory biomarkers are known to emerge years before a definitive diagnosis of rheumatoid arthritis is possible. 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.

Dysbiosis and RA:

Cross-sectional, human gut microbiome studies have elucidated the potential role of gut microbiome “dysbiosis” in RA (2). A study that compared RA patients' gut microbiome to that of healthy controls showed that the richness and diversity of intestinal flora in RA patients were impaired. This could be responsible for the pathogenesis of RA by modulating the immune systems with lymphocyte subpopulations and cytokines (3).

Healthy gut virome, significantly decreased in the gut of the patients with autoimmune diseases, specifically the patients with RA and SLE. Higher levels of gingival disease and unhealthy oral microbiota are also associated with the early stage of RA(3). The gut microbiome is now considered an important immune organ and plays an indispensable role in immune response and tolerance.

Gut bacteria and RA outcomes:

The gut microbiome is increasingly considered to be involved in the processing of various exogenous substances and can also influence host responses to various drugs (medications) (4).

A study published in Genome Medicine found that a patient’s gut microbes at baseline and their outcome of RA may be connected. By looking at patients’ baseline gut microbiome profiles, the researchers observed significantly different microbiome traits between patients who eventually showed clinical improvements and those who did not.

In a recent editorial in Arthritis & Rheumatology, Dr Renuka Nayak states “The findings leave open the possibility that the microbiome can either add fuel to the fire of autoimmunity over the course of a lifetime or can reduce the level of autoimmunity and progression of disease. These questions are of clinical relevance because while modifying the human genome is challenging, altering the human microbiome via diet, supplements, probiotics, and medications is more feasible.”

RA Medications and gut microbiome:

The gut microbiome can affect the bioavailability of Methotrexate and some characteristics of gut microbiome can be considered as a predictor of clinical response of this drug. In addition, gut microbiome is associated with adverse reactions to Methotrexate, especially gastrointestinal reactions. Methotrexate also affects the amount, diversity, and major components of the gastrointestinal microbiota (6).

Microbial differences found in the gastrointestinal tract of RA patients may partially determine the bioavailability and/or subsequent clinical outcome of Methotrexate.

A recent study found that the intestinal absorption and metabolism of Methotrexate in germ-free and antibiotic-treated mice were reduced compared to wild-type mice, suggesting that the biotransformation of Methotrexate was hindered if the microbiome was not present, that is, gut microorganisms is an essential link in the absorption and metabolism of Methotrexate. At the phylum level, the ratio of Firmicutes/Bacteroidetes in Methotrexate - Non Responders is high. By contrast, in MTX-Responders, Prevotella and Bacteroides genera are significantly more abundant (6).

Side Effects due to Methotrexate:

The latest international view suggests that the mechanism of folic acid supplementation to reduce the toxic effect may also be related to intestinal flora, especially the probiotics such as Bacteroides and Bifidobacterium. Both diet and Leucovorin reduce gastrointestinal toxicity by affecting the gut microbiome. And it has previously been reported that artificially increased probiotics intake or the use of fecal microbiota transplantation (FMT) ameliorates drug-induced intestinal damage.

What does all of this mean for you?

Here are the main takeaways as I see it:

Gut health is important as it can have an impact on your disease severity as well as outcomes of medications.
In addition, improving your gut health can reduce the side effects of your RA medications.
Continue to work on your gut health by making important dietary and lifestyle changes. I strongly recommend starting with the AIP diet first to start healing the gut and overcoming food sensitivities (which most people with RA have).
Adding a probiotic supplement (Bifido) can help. However, the best way to increasing the diversity and richness of your gut flora is by eating a variety of fermented foods.