The mysterious microbial world within us is beginning to reveal its secrets, but many mysteries remain to be solved in the years to come. Dr. Diane Mathis
The gut continues to surprise. This study is on rheumatoid arthritis, but you might want to just replace RA with the term ‘autoimmune disorder’ because this study, one of the most comprehensive of its type, demonstrates how changes in gut flora may be associated with development of an autoimmune disorder.
The immune system may be presented with its greatest test of all with the gut as it determines which of the hundreds and perhaps thousands microbial species in our guts are helpful and which are harmful. If the immune system mistakes a human antigen for one of the ‘bad guys’ it will attack the body possibly causing devastating disorders like rheumatoid arthritis.
In other words, the complex microflora in our guts may give the immune system more opportunities to fail than anywhere else in the body.
Studies have shown that an autoimmune state with circulating auto-antibodies and increased pro-inflammatory cytokines is usually present for ‘many years’ before people with RA show any signs of disease. This pre-clinical state appears to set the stage for an environmental event very possibly featuring microbes that trigger a systemic attack on the joints.
The microbiome or intestinal flora clearly plays a role in establishing arthritis in animal models. Now it was time examine it’s role in humans with rheumatoid arthritis (RA).
Before we start, let’s note that an online check suggested that gut symptoms are not common in RA; i.e., the gut could play a major role in RA without producing any symptoms at all.
This study examined the gene sequences of 144 fecal samples from new onset RA patients, other RA patients, psoriatic arthritis patients and healthy controls.
One Gut Species Dominates Gut Flora in New Rheumatoid Arthritis Patients
The gut flora of new rheumatoid arthritis patients was ‘defined’ by a single taxon, Prevotella copri. P. copri was also found in lower amounts in healthy controls, treated RA patients and psoriatic arthritis patients, but only the flora of the new onset RA patients was ‘defined’ by a single bacterial species. Beneficial bacteria (Bacteroides, Lachnospiraceae, and Clostridia) were reduced.
Seventy-five percent of stool samples from patients newly diagnosed with rheumatoid arthritis carried P. copri compared to 21.4% of samples from healthy individuals; 11.5% from chronic, treated patients; and 37.5% from patients with psoriatic arthritis.
Interestingly, P. copri levels were normal in treated RA patients, suggesting that anti-inflammatory drugs created a less than optimum environment for the bacteria.
The ability of P. copri to dominate the flora of mice, just two weeks after it was injected into them, suggested that in the right conditions it was remarkably aggressive.
An examination of P. copri’s enzymatic pathways suggested the bacteria could be hurting RA patients in other ways. It turns out that P. copri turns off metabolic factors that break down methotrexate. P. copri may then, not only may be able to initiate RA, but it may inhibit one of the major treatments for it.
Some studies suggest that that environmental event that turns pre-clinical signs of autoimmunity into a systemic attack on the joints may feature bacteria found in the mouth (periodontal areas), the airways or the gut. Prior to this study, Prevotella has mainly been associated with periodontal disease. (Keep your gums healthy!)
Getting From the Gut to the Joints (or Elsewhere)
The ability of the gut to strongly influence parts of the body outside the gut is still raising eyebrows in the medical community. In an accompanying editorial, Dr. Diane Mathis stated
“While it is not very surprising that intestinal bacteria affect susceptibility to and/or the severity of autoimmune disorders localized to the gut—notably inflammatory bowel disease—their ability to profoundly impact other immune disorders, including arthritis (Wu et al., 2010), experimental allergic encephalomyelitis (Lee et al., 2011) and type-1 diabetes (Kriegel et al., 2011), came as a surprise.”
One of the more intriguing aspects of the study were findings concerning c-reactive protein, which appears to be increased in ME/CFS, and the HLA axis, which is currently undergoing investigation in ME/CFS. Very high levels of C-reactive protein were found in the P. copri dominated RA patients, and introducing HLA alleles associated with an increased risk of getting RA into mice had ‘a profound impact’ on their gut flora and affected their gut permeability.
The immune/gut interface is growing stronger and stronger. The gut certainly influences and may cause RA and Dr. Ian Lipkin believes it may hold the key to ME/CFS as well.
The association between P. copri and RA is just that, right now – an association. Further studies are needed to determine if it plays a role in causing it.
The study was enough, though, for some to be looking to the future of gut manipulation to treat RA and other disorders.
“The clinical implication of this is that if we can find ways to manipulate the intestinal microbiome, we may be able to have an impact on a number of diseases, including rheumatoid arthritis. That could be through diet, targeted antibiotic therapy, or by the provision of ‘good’ bacteria that might displace the Prevotella, which appears to be associated with the development of rheumatoid arthritis”
From autism to ME/CFS to autoimmune disorders, the gut and gut manipulation are getting more interest. We’re waiting for the publication of the CFIDS Association funded gut study, and Dr. Lipkin has called for a major ME/CFS gut flora study. On Health Rising look forward to more from Ken Lassesen and a blog on ‘Healing the Gut’ from Niki Gratrix in the near future.
Department of Medicine, New York University School of Medicine and Hospital for Joint Diseases, New York, United States.