Another Step Forward: Ankylosing Spondylitis and the Microbiome

The evidence continues to mount pointing to microbiome alterations as being (one of?) the underlying cause of ankylosing spondylitis (AS).  Just a few weeks ago, I wrote about a long-term study on 150 patients with AS which showed distinct alterations in the biome.  A second major paper (out of China) appeared in the Journal of Autoimmunity within the last few weeks which moved the research forward once again.[i]

I’ve pointed out in previous posts about AS that “…at least 2.7 MILLION people suffer from these diseases in the USA alone, which is almost 3X the number of people that suffer from the way better known Parkinson’s disease alone…”  This is an illness that affects millions of people at yet, remains relatively unknown and unstudied.  Worse still, it typically takes years to be diagnosed, leaving many people untreated and suffering.  I am always really happy when I see some new information about it.

In this recent paper, the scientists looked at the fecal microbiome of 108 people with AS, 85 of whom were untreated, the other 23 of whom were undergoing treatment.  They also had feces from 62 healthy controls.

They did multiple tests which provided a great deal of new data:

1.  They confirmed that specific bacterial species are at higher levels in those with untreated AS when compared to healthy controls.  These species include Bacteroides coprophilus, Parabacteroides distasonis, Eubacterium siraeum, Acidaminococcus fermentans and Prevotella copri.  Levels of other bacteria were lower than controls, including Enterococcus faecium.
2. When patients with AS are treated, levels of some bacteria began to resemble those of healthy controls: Prevotella levels decreased and Enterococcus faecium increased:  “…the facts  above indicate a possible causal relationship between Prevotella copri and AS pathogenesis.”  The shift in this bacterial species toward control levels was more marked with immune-suppressant medicines than with just NSAIDS (non-steroidal anti-inflammatories, like ibuprofen).
3. Several pathways associated with the microbiome are altered in those with AS, including one that may lead to bone destruction and compromise gut wall integrity.
4. The pattern of bacterial alterations in those with AS is distinct enough that it looks like it will be able to be used diagnostically. This is really good news, in that, as mentioned above, diagnosis of the condition typically takes YEARS, leaving people untreated, or inappropriately treated, which of course leads to further bone deterioration.
5. A quick definition for anyone unfamiliar:  molecular mimicry encompasses the idea that foreign proteins may look an awful lot like our bodies’ own and thus, we form autoantibodies to both, leading to autoimmune disease.  These researchers found 3 peptides (which are just short proteins) “…among bacterial species enriched in AS patients that are similar to auto-antigens with a known role in AS.”  In fact, one of these peptides “…stimulated secretion of the pro-inflammatory molecule IFN-gamma by immune cells in AS patients, but not in controls.”[ii]  This peptide mimics one found in collagen, which is the main component of cartilage.  As the body attempts to destroy the foreign invader, it ends up attacking its own cartilage.

The conclusion remains that “Despite the fact that several gut microbiota studies have been performed in AS patients, we are still far from a clear causality between gut dysbiosis and AS pathogenesis. Unlike other inflammatory diseases such as RA whose development have been proven to partially attribute to gut dysbiosis, the exact relationship between any specific microbial taxa and AS pathogenesis has not been reported yet.”  So way more still needs to be done.

Still, this year already we’ve seen two major steps forward in research.  And that is, at least, of some comfort.

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[i] Zhou, C, et. al. Metagenomic profiling of the pro-inflammatory gut microbiota in ankylosing spondylitis. Journal of Autoimmunity. 2019. DOI: 10.1016/j.jaut.2019.102360

[ii] https://ankylosingspondylitisnews.com/2020/01/23/gut-microbiome-in-ankylosing-spondylitis-patients-is-imbalanced-and-contributes-to-inflammation/