Relationship Bowel/Arthritis: What we know so far

Herman Mielants is a Belgian Rheumatologist who is especially interested in the link between intestinal inflammation and arthritic conditions. Herman’s research over the last 30 years allowed us to better understand the connection between damage to the intestinal wall and the development of several rheumatic conditions. In his studies, he performed colonoscopies to his patients, even in the absence of gastrointestinal symptoms. The results were absolutely shocking: more than 60% of patients with Spondylarthropathies such as Ankylosing Spondylitis or Reactive Arthritis had inflammation in their large bowel, predominantly in the Ileum. Two histological types of gut inflammation can be distinguished in spondyloarthropathies, i.e. acute and chronic, based on their morphological characteristics, not on the time of onset or duration of the disease. Contrary to that, healthy people and patients with other inflammatory conditions such as Rheumatoid arthritis or Lupus didn’t show inflammation in the large bowel. That would explain why these patients respond less to dietary changes than those who have axial arthritis.

Model of Reactive Arthritis in a HLA B27 positive patient

The acute type resembles acute bacterial enterocolitis, with a well-preserved mucosal architecture. The chronic type resembles chronic ileocolitis and is generally indistinguishable from Crohn’s disease, with a clearly disrupted mucosal architecture. While acute lesions are mainly seen in patients with reactive arthritis, chronic lesions are more prevalent in undifferentiated spondyloarthropathies and ankylosing spondylitis. Only 27% of patients with histological gut inflammation have intestinal symptoms. However, more than 30% of them will develop IBD, more commonly Crohn’s disease. What is more astonishing is the fact that, after some years, a second colonoscopy showed that patients who were in remission, didn’t have inflammation in the bowel. The relationship seems obvious. There are also other interesting findings. For example, the degree of inflammation in the sacroiliac joints is correlated with the inflammation seen in the gut. Furthermore, Budesonide, an intestinal corticosteroid that is linked to less adverse events than prednisone, gives similar results in axial arthritic conditions.

Many different strains may produce ReA. In other axial arthritic conditions normal bowel flora may be the culprit

We emphasize that all patients with axial arthritis should be checked for intestinal damage in order to receive adequate treatment before IBD development (when it is suspected).

As there’s clear Crohn’s-like bowel envolvement in these diseases, Mielants investigated whether IBD markers would be raised in axial arthritis. As in Crohn’s disease, anti Saccharomyces cerevisiae antibodies are raised in axial arthritis. Fecal Calprotectin fCAL, usually checked in IBD patients,  can be used to identify and characterize a subgroup of AS patients whose disease might be driven by subclinical bowel inflammation. Mielants also observed a greater gut permeability in rheumatic patients irrespective of whether they were taking non-steroidal anti-inflammatory drugs, indicating that the disrupted permeability is disease-related.

Now, is there any great marker of axial arthritis associated to intestinal inflammation? The ideal marker should be easy to test, repeatable and inexpensive. Currently used blood markers are non-specific and reflect both joint and intestinal inflammation. The fecal markers calprotectin and lactoferrin, and intestinal permeability are more promising tests, as they have a good specificity for intestinal disorders and are straightforward to perform. This is very important, particularly to pinpoint those patients without intestinal symptoms who need to be selected for further, more invasive investigations, and to avoid medication-related complications.

Taking into account this correlation, the most plausible theory is the one proposed by Fassano, who suggests that in axial arthritis, Intestinal tight junction dysfunction allows bacterial traslocation to host’s joints, starting an uncontrolled immune reaction against the spine. This new theory implies that once the pathologic process is activated, it is not auto-perpetuating. Rather it can be modulated or even reversed by preventing the continuous interplay between genes and the environment. That’s what several approaches such as diethetic modifications, drugs and supplements will have to address in the future.

We recommend reading Ballantyne’s book, where this theory is perfectly explained: