ROCHESTER, Minn. – The bacteria in your gut do more than break down your food. They also can predict susceptibility to rheumatoid arthritis, suggests Veena Taneja, Ph.D., an immunologist at Mayo Clinic’s Center for Individualized Medicine. Dr. Taneja recently published two studies — one in Genome Medicine and one in Arthritis and Rheumatology — connecting the dots between gut microbiota and rheumatoid arthritis.
More than 1.5 million Americans have rheumatoid arthritis, a disorder that causes painful swelling in the joints. Scientists have a limited understanding of the processes that trigger the disease. Dr. Taneja and her team identified intestinal bacteria as a possible cause; their studies indicate that testing for specific microbiota in the gut can help physicians predict and prevent the onset of rheumatoid arthritis.
“These are exciting discoveries that we may be able to use to personalize treatment for patients,” Dr. Taneja says.
The paper published in Genome Medicine summarizes a study of rheumatoid arthritis patients, their relatives and a healthy control group. The study aimed to find a biomarker — or a substance that indicates a disease, condition or phenomena — that predicts susceptibility to rheumatoid arthritis. They noted that an abundance of certain rare bacterial lineages causes a microbial imbalance that is found in rheumatoid arthritis patients.
“Using genomic sequencing technology, we were able to pin down some gut microbes that were normally rare and of low abundance in healthy individuals, but expanded in patients with rheumatoid arthritis,” Dr. Taneja says.
Implications for predicting and preventing rheumatoid arthritis
After further research in mice and, eventually, humans, intestinal microbiota and metabolic signatures could help scientists build a predictive profile for who is likely to develop rheumatoid arthritis and the course the disease will take, Dr. Taneja says.
Based on mouse studies, researchers found an association between the gut microbe Collinsella and the arthritis phenotype. The presence of these bacteria may lead to new ways to diagnose patients and to reduce the imbalance that causes rheumatoid arthritis before or in its early stages, according to John Davis III, M.D., and Eric Matteson, M.D., Mayo Clinic rheumatologists and study co-authors. Continued research could lead to preventive treatments.
Possibility for more effective treatment with fewer side effects
The second paper, published in Arthritis and Rheumatology, explored another facet of gut bacteria. Dr. Taneja treated one group of arthritis-susceptible mice with a bacterium, Prevotella histicola, and compared that to a group that had no treatment. The study found that mice treated with the bacterium had decreased symptom frequency and severity, and fewer inflammatory conditions associated with rheumatoid arthritis. The treatment produced fewer side effects, such as weight gain and villous atrophy — a condition that prevents the gut from absorbing nutrients — that may be linked with other, more traditional treatments.
While human trials have not yet taken place, the mice’s immune systems and arthritis mimic humans, and shows promise for similar, positive effects. Since this bacterium is a part of healthy human gut, treatment is less likely to have side effects, says study co-author Joseph Murray, M.D., a Mayo Clinic gastroenterologist.
Rheumatoid arthritis is an autoimmune disorder; it occurs when the body mistakenly attacks itself. The body breaks down tissues around joints, causing swelling that can erode bone and deform the joints. The disease can damage other parts of the body, including the skin, eyes, heart, lung and blood vessels.
Creapharma.com interviewed Dr. Taneja:
In your first study published in Genome Medicine, the study was only carried out on mouses or also on humans?
The study in Genome Medicine was carried out in humans. Using recent technology of genome sequencing, we showed a lower diversity of the gut microbiota in patients with Rheumatoid Arthritis as compared to the first degree relatives and healthy individuals in our study. Our study suggested that some bacteria that are present in very low numbers in healthy individuals have expanded in patients. Using algorithms, we could show 2 bacteria that were in high numbers in patients but not in healthy individuals. One bacteria which is considered good for the health of our gut and is generally abundant in healthy individuals was present in low numbers in patients.
We tested pathogenicity of one of the bacteria that was identified in patients in mice carrying human RA-susceptible gene. Mice given bacteria present in RA patients developed severe arthritis with a leaky gut suggesting this to be a pathogenic bacteria.
In addition, we have identified a bacteria, Prevotella histicola, from the upper gut from human biopsy which is beneficial for suppressing inflammation. In our study that was recently published in Arthritis Rheumatology, we treated arthritic mice, who have been modified to have the human arthritis-susceptible gene, with Prevotella histicola. Mice that were treated with this bacteria did not develop severe arthritis and fewer mice developed arthritis as compared to arthritic mice not treated with this bacteria.
Do you think your first study could lead soon to new diagnostic methods? Do you have any idea in how many years we might have these tools on the market?
We are working to validate findings in a bigger sample set. We believe that microbial profile, along with the other known factors, may be able to predict risk as well characterize why some individuals develop severe arthritis while others do not. Each individual has a unique composition of bacteria and that could also be the reason why one drug does not work for all. Lot of work is still needed to uncover how best we can use this information.
In a study and an interview our media did in the last weeks (more information here) Prof. Maureen R. Hanson and her team from Cornell University who studied chronic fatigue syndrome (CFS) and the microbiome said that some gut bacteria like E. coli could stimulate the immune system to react, potentially causing some of the illness symptoms experienced by patients suffering from CFS. Do you think that one cause of rheumatoid arthritis could also be in the gut (in the microbiome) or do you think it might be more a consequence of RA, other said RA could lead to altered gut microbiome? It seems that your second study published in Arthritis and Rheumatology goes more in the direction that some gut bacterias could be a cause of RA, perhaps trigger inflammation?
Our study and others show that the gut microbiome plays a critical role in pathogenesis of RA. Whether the altered gut microbiota is a cause or consequence needs to be examined. The best way of doing that is by using first degree relatives and families with multiple autoimmune diseases and using mouse models as in humans the altered immune response precedes clinical symptoms. Altered microbiota with expanded pathogens or opportunistic bacteria may contribute to inflammation thus exacerbating disease severity.
We see many studies now published about microbiome, in a Tweet the famous American cardiologist Eric Topol, mentionned that fact in the last days. From fatigue now to PR, isn’t there a risk to exagerate the influence of microbiome for being the cause of so many diseases? Or do you think that understanding better the microbiome is almost a revolution for the future of medicine and it will lead to very innovative treatments?
I believe that microbiome has a strong influence on immune system. Our study in genome medicine and other studies have documented the importance of microbiome in diseases. Further, our study in Arthritis Rheumatology suggests that a good microbe may help in suppressing inflammatory immune response thus stopping progression of arthritis.
The fact that microbiome may be involved is not new as the importance of diet in human health was known centuries ago. According to ancient texts of Indian Ayurveda, when consumed properly, food is like a medicine for the body. Food has a big impact on the kind of bacteria colonizing the gut. The potential of the gut microbiome and its impact on diseases has been realized recently due to technological advances.
July 14th 2016. Source: Press Release, interview run by Xavier Gruffat (Pharmacist ETH Zurich, Switzerland) between July 11th and July 14th 2016. Pictures: Fotolia.com
