The last time I wrote about research on the biome and rheumatoid arthritis was last February so it’s about time for something new and exciting. A paper was just published by researchers at the University College London that shows that bacterial dysbiosis may lead to damage to the lining of the gut, which correlates to joint inflammation and the severity of arthritic disease: “…in arthritis, there is profound damage to the gut lining, which fails to work properly as a barrier, as well as an accumulation in the gut of white blood cells that cause inflammation. The authors show that, in arthritis, bacteria cross the prohibited border of the intestinal lining and that repairing gut permeability defects with specific drugs inhibits joint inflammation.”[i]
Their research shows, firstly, that mice bred to be genetically predisposed to have gut permeability (leaky gut) developed severe arthritis. In a different type of mouse, engineered to develop collagen-induced arthritis, reducing leaky gut resulted in reduced joint inflammation. They then looked at humans: those with RA have increased levels of lipopolysaccharide (LPS, which is a toxic metabolite from certain types of gut bacteria) was found in their blood, as were two other significant molecules: LPS binding protein and intestinal fatty acid binding protein. All three are markers for intestinal damage (compromised epithelial barrier integrity) and the scientists found that the blood level of these molecules correlated with disease severity: “RA patients display increased levels of serum markers of gut permeability and damage and cellular gut-homing markers, both parameters positively correlating with disease severity.”
Science has already shown that those with RA have abnormal gut bacteria. For example, high levels of Collinsella aerofaciens, bacteria which is known to increase gut permeability, has been found in the population. The mice in these experiments had markedly increased Prevotella and reduced Lactobacillus, which, interestingly, became more pronounced as the disease progressed. Also of note: some treatments currently used for RA, including NSAIDS (non-steroidal anti-inflammatory drugs), are known to increase gut permeability.
Now for some good and genuinely hopeful news:
Treating arthritic mice with a molecule called AT-1001, which is known to reduce intestinal barrier permeability, ameliorated the arthritis. I looked it up and found out that AT-1001, also known as larazotide acetate, appears to currently be in phase 3 clinical trials for celiac disease, via the company 9 Meters Biopharma, located in Raleigh, NC. “Larazotide acetate is designed to tighten the adhesions between cells lining the small intestine, called tight junctions…This ‘leaky gut’ is thought to be the gateway to many autoimmune diseases, including celiac disease. Larazotide acetate makes the tight junctions more secure, keeping gliadin from passing through.”[ii] The authors of this RA paper state that because of this effect, it may prove very useful in rheumatic diseases as well.
The conclusion: “We suggest that breakdown of gut-barrier integrity contributes to arthritis development and propose restoration of gut-barrier homeostasis as a new therapeutic approach for RA.” Perhaps help is really on the horizon.
[i] Matei, DE, et. Al. Intestinal barrier dysfunction plays an integral role in arthritis pathology and can be targeted to ameliorate disease. Med. 2021. 9(7):864-883. doi: 10.1016/j.medj.2021.04.013..