Inflammatory Arthritis and the Gut
I’ve been keeping an eye out for anything new and interesting in the realm of the biome and arthritis – any kind of arthritis. Following are some highlights from a recent article on the two way communication between the gut immune system and the resident bacteria, and its association to rheumatoid arthritis (RA), osteoarthritis (OA), and inflammatory spondylitis (SpA) conditions like psoriatic arthritis and ankylosing spondylitis.[i]
The authors start by emphasizing that while exact mechanisms of action are as yet unknown, evidences continues to mount that these illnesses are directly related to alterations in the gut bacteria, and that those alterations are may well be causative.
- 70% of the immune system is located in the gut. And there is sufficient data to establish that communication between that immune system and the microbiota, “…promotes intestinal barrier integrity, supports the functional capacity of the gut epithelium, protests from pathogens and maintains the immune homeostasis in the gut.”
- Rheumatoid arthritis: Recent research has shown that years before arthritic changes become evident, dysbiosis has been found to be present, “…suggesting an important role of microbiota in the transition from the preclinical to the clinical stage of RA.” The most accepted current hypothesis is molecular mimicry, meaning that the antibodies created by the immune system to fight off a pathogenic bacteria mistakenly mark body tissue for destruction. Programmed cell death (apoptosis) of infected colon cells is known to create antibodies to both the pathogenic bacteria, Citrobacter rodentium, and autoreactive antibodies, and concurrent inflammation. P. corpi is a bacteria of particular interest in that two RA-specific autoantibodies are very similar to those formed to battle this bacteria. The same with a particular yeast, Collinsella aerofaciens.
- Notable differences are found in the composition of the gut flora between those with RA and SpA.
- Here are some remarkable SpA statisics: as many as 10-15% of those with SpA go on to develop inflammatory bowel disease (IBD), and conversely, 30% of IBD patients will develop SpA. That astounds me. 50% of those with SpA who do not have GI symptoms still test positive for microscopic intestinal inflammation. As mentioned in #4, those with SpA have major differences in gut microbiome composition: for example, Akkermansia and Ruminococcous, which are important in gut health, are almost non-existent in these patients.
- While not firmly established, there is a growing belief in a causal relationship between these alterations and SpA-family disease. Rodents genetically predisposed to spontaneously develop SpA do not do so when kept in a germ-free environment, so they have no gut bacteria. Give them some of the altered gut flora though from the same type of mouse with SpA…and they rapidly develop the disease.
- Chronic, low-grade inflammation and obesity are already recognized causes of osteoarthritis. Several pieces of evidence show that the gut bacteria play a pivotal role in causing and maintaining this systemic and gut inflammation.
- Probiotics: we’re not there yet. In an animal model, Lactobacillus casei showed clear anti-arthritic activity. However, the human clinical studies have been too small and short-term to produce any kind of consistent or meaningful results in treating either RA or SpA. In osteoarthritis, however, some success has also been seen in rodents.
- Prebiotics: again, we are plagued with inconsistent results in trying to treat any of these arthritis diseases in humans. In rodents, supplementing obese mice with OA with oligofructose led to higher levels of Bifodobacteria, which in turn led to improved gut health, and a reduction of inflammation, including in the joints of the animals. These results were consistent with some of the things seen in overweight humans (in a double-blind, placebo controlled study) when treated with the same: they lost weight and had lower levels of toxic bacterial byproducts in their blood, demonstrating improved intestinal barrier function.
These authors conclude that it is now clear that “…unfavorable dysbiosis-mediated immune alterations precede the development of these disorders, suggesting causal relationships in this link [between the microbiota and the immune system].” This is exactly the same phenomenon I described on Tuesday, seen in those with Parkinson’s.
We have to hope that soon there will be regular testing of our biomes. Perhaps if we can catch these changes early on, someday soon we’ll be able to prevent all these diseases from developing in the first place.
[i] Kalinkovich, A, and Livshits, G. A cross talk between dysbiosis and gut-associated immune system governs the development of inflammatory arthropaties. Seminars in Arthrisi and Rheumatism. 2019; 49 (3), 474-484. DOI: 10.1016/j.semarthrit.2019.05.007