ROCHESTER, Minn. — A significant indicator of whether a patient with rheumatoid arthritis will improve over the course of disease may lie in part in their gut, according to new research from Mayo Clinic's Center for Individualized Medicine.

The study, published in Genome Medicine, found that predicting a patient's future rheumatoid arthritis prognosis could be possible by zeroing in on the trillions of bacteria, viruses and fungi that inhabit their gastrointestinal tract, known as the gut microbiome. The findings suggest that gut microbes and a patient's outcome of rheumatoid arthritis are connected.

"This is the first study to date that uses gut microbiome data to predict clinical improvement in rheumatoid arthritis disease activity independent of the initial measurement of their condition or prior treatment," says Jaeyun Sung, Ph.D., a computational biologist within Mayo Clinic's Center for Individualized Medicine and co-senior author of the study.

Rheumatoid arthritis is a chronic disorder characterized by joint inflammation and pain that can eventually lead to bone and cartilage erosion, joint deformity and loss in mobility. This complex disease affects nearly 1.3 million people in the U.S.

Zeroing in on the microbiome

For the study, the team performed a comprehensive precision genomic analysis, called "shotgun metagenomic sequencing," on stool samples from 32 patients with rheumatoid arthritis at two separate clinical visits. The team investigated the connection between the gut microbiome and the smallest meaningful changes in clinical disease activity. The team found several traits of the gut microbiome linked to future prognosis.

"By looking at patients' baseline gut microbiome profiles, we observed significantly different microbiome traits between patients who eventually showed improvement and those who did not," says John M. Davis III, M.D., a clinical rheumatologist at Mayo Clinic with a specialty interest in inflammatory arthritis. Dr. Davis is co-senior author of the study.

"What was surprising is that our data suggest that depending on the eventual clinical outcome, gut microbiomes not only start at different ecological states, but also grow and develop differently," Dr. Sung adds.

Next, by using deep-learning artificial intelligence (AI), the investigators examined if they could predict whether a patient achieves clinical improvement. Overall, the predictive performance resulted in 90% accuracy, thereby showcasing the proof of concept that the integration of gut microbiome and AI technology could theoretically be an avenue to predict disease course in rheumatoid arthritis.

Path toward treatment

"With further development, such prognostic biomarkers could identify patients who will achieve early clinical improvement with a given therapy, thereby sparing them the expense and risk of other therapies that are less likely to be effective," Dr. Davis says. "Conversely, such tools can detect patients whose disease symptoms are less likely to improve, and perhaps allow clinicians to target and monitor them more closely. Much is left to be done, but we're on the right path toward advancing our understanding of this disease in order to individualize medicine for patients with rheumatoid arthritis."

Scientists have suspected for some time that the gut microbiome plays a role in rheumatoid arthritis, as well as many other inflammatory and autoimmune diseases. The enormous population of microbes help digest food, regulate the immune system and protect against pathogenic bacteria.

The researchers emphasize that every person's microbiome is unique and consists of a complex mix of genetic, dietary and environmental influences. These differences shed light on why symptoms vary significantly among rheumatoid arthritis patients, which in turn makes it so difficult to treat and predict clinical outcome.

The study is the second recent rheumatoid arthritis investigation by Drs. Sung and Davis, highlighting the essential partnership between computational biologists and clinicians to solve complex problems in medicine. Together, they are on a path toward developing a suite of new data-driven tools to aid in early detection, diagnosis, prognosis and treatment in rheumatoid arthritis. As such, the researchers plan to explore ways to translate their findings into new biomarkers and therapies.

"Ultimately, our study reveals that modifying the gut microbiome to enhance clinical outcome may hold promise as a future treatment for rheumatoid arthritis," Dr. Sung says. "This could revolutionize how we deliver care to our patients."

This work was supported in part by Mayo Clinic's Center for Individualized Medicine and Mark E. and Mary A. Davis.

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ANSWER: It’s possible that the stiffness in your fingers could be related to arthritis. If the discomfort is disrupting your daily routines — or if the symptoms get worse or you notice new ones — it would be a good idea to see your primary care physician for an evaluation. Treatment for arthritis is available, although specific treatment options depend on the diagnosis.

There are two basic types of arthritis: osteoarthritis and rheumatoid arthritis. Osteoarthritis is, by far, the most common. It often develops as people age, when the protective cartilage on the ends of the bones wears down over time. Osteoarthritis leads to joint pain, tenderness, stiffness and loss of flexibility.

Rheumatoid arthritis is an autoimmune disease in which the body’s immune system attacks the synovium, the lining of the membranes that surround the joints. It causes chronic inflammation, along with joint pain, swelling and stiffness. In some people, rheumatoid arthritis eventually can lead to joint damage and disability.

Despite the fact that their symptoms may be similar, the two forms of arthritis differ significantly from one another and require different forms of treatment. Seeing a health care professional early is a good idea, as some of the treatments can affect the natural progression of the condition.

Rheumatoid arthritis typically affects the small joints first, particularly those that connect the fingers to the hands and the toes to the feet. Early-warning signs of rheumatoid arthritis include joint swelling, especially in the knuckles at the base of the fingers, or in the wrists or feet; stiffness of the hands, wrists or feet that occurs in the early morning and improves after activity; and unexplained fatigue, fever or weight loss.

Even if your symptoms don’t match any of those on that list, it still is reasonable to consult with your health care provider if the stiffness in your fingers is bothersome to you or if it’s making it hard for you to do your daily activities. Let your health care provider know if you have a parent, sibling or child with rheumatoid arthritis, which means you may have an increased risk of the disease.

Your health care provider can assess your situation and, if necessary, recommend a treatment plan based on your circumstances. Neither form of arthritis can be cured, but treatment often can help control symptoms.

Treatment for osteoarthritis generally includes pain medication, physical therapy and, in some cases, corticosteroid injections. Modifying activities to reduce stress on the joints often is necessary, as well.

For rheumatoid arthritis, treatment involves medication to reduce inflammation, as well as drugs to slow the progression of the disease and reduce joint damage. Medication that targets the immune system also may ease inflammation, and lower the risk of joint and tissue damage. Physical and occupational therapy can be useful for people who have rheumatoid arthritis.

At this point, though, the first step is to assess your symptoms and decide if you want to get an evaluation. If so, your health care provider can perform a physical exam, review your medical history and, if necessary, recommend testing to investigate the underlying cause of your joint stiffness. If a medical condition is found, treatment can be customized to fit your individual needs. — Dr. John Davis III, Rheumatology, Mayo Clinic, Rochester, Minnesota

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DEAR MAYO CLINIC: My mother, 70, has osteoarthritis and was prescribed medication to help with the pain. What else can she do to keep it from worsening? Is physical therapy an option?

ANSWER: Osteoarthritis is a progressive disease that slowly gets worse over time. Although the process of osteoarthritis can’t be reversed, the symptoms usually can be effectively managed. Medication helps. Exercising regularly, staying at a healthy weight and lowering stress on joints makes a difference, too. For many people who have osteoarthritis, physical therapy is a useful part of their treatment plan.

Osteoarthritis happens when the protective cartilage that cushions the ends of bones in joints gradually breaks down. That leads to joint pain, tenderness and stiffness. Although osteoarthritis may damage any joint, it’s most common in the hands, knees, hips and spine.

As in your mother’s situation, medications such as acetaminophen and nonsteroidal anti-inflammatory drugs, or NSAIDs, frequently are used to control osteoarthritis. Several topical medications are available that can reduce joint pain, too. They include, among others, capsaicin cream and a gel form of the NSAID ibuprofen.

Exercising on a regular basis also helps ease osteoarthritis symptoms. This is where physical therapy may be useful. A physical therapist can work with your mother to create an individual exercise program to strengthen the muscles around her joints, increasing her range of motion and reducing pain.

Low-impact exercises, such as swimming, biking and walking, usually work well. Some people also enjoy activities such as tai chi and yoga, which combine gentle exercises and stretching with deep breathing. A physical therapist can help your mother decide on the activities that are right for her.

Staying at a healthy weight also is an important part of managing osteoarthritis. Carrying extra weight increases the stress on weight-bearing joints, such as the knees and hips. Even a small amount of weight loss can relieve some pressure and decrease pain. If she would like to lose weight, your mother can ask her health care provider for a referral to a dietitian. He or she can discuss healthy weight-loss strategies, offer suggestions for meal planning and provide your mother with nutritious recipes to get started.

To keep her symptoms from getting worse, your mother should try to avoid overusing the joints affected by osteoarthritis. A variety of assistive devices are available that can make everyday tasks less stressful on joints. For example, using a cane takes weight off a painful knee or hip. Gripping and grabbing tools make it easier to open doors and jars. Encourage your mother to ask her health care provider for information about these and other assistive devices that might be useful for her.

Some forms of alternative medicine have been suggested for osteoarthritis treatment, too. Acupuncture — a technique that involves inserting extremely thin needles through the skin at strategic points on the body — may contribute to pain control for some people. Meditation may also ease osteoarthritis symptoms in certain cases.

The nutritional supplements glucosamine and chondroitin often are touted as effective treatment for osteoarthritis. Results from studies on these nutritional supplements have been mixed though. A few have found benefits for people with osteoarthritis, but most have shown no clear effects. If your mother is interested in trying these supplements, encourage her to talk with her health care provider first. Glucosamine is not safe for people who are allergic to shellfish. Also, glucosamine and chondroitin may interact with blood thinners, such as warfarin, and cause bleeding problems.

Before she goes forward with any additional treatment, it would be a good idea for your mother to make an appointment to see her health care provider, talk about her options and discuss the benefits and risks of each. From there, they can create a comprehensive treatment plan that will help keep your mother’s osteoarthritis symptoms under control. — Dr. John Davis III, Rheumatology, Mayo Clinic, Rochester, Minnesota

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