Scientists can’t predict what triggers rheumatoid arthritis, a mysterious and painful autoimmune disorder that causes inflammation in the joints. But they’re targeting an intriguing new suspect: the trillions of microbes living and working inside the gut.
Animal models have long suggested that intestinal bacteria can influence the development of some autoimmune diseases. This may also be the case with rheumatoid arthritis, according to emerging research, a finding that could lead to novel treatments and diagnostic methods.
Though long ignored by researchers, “these bacteria clearly exert a great deal of influence on many physiological processes in the body, including metabolism, digestion and the nutrients we take in,” said Dan Littman, professor of pathology and microbiology at the New York University School of Medicine and an investigator at the Howard Hughes Medical Institute. “The part that’s less appreciated is the profound influence the microbiota can have on the immune system.”
Bacteria and other microbes, such as viruses and fungi, form the microbiota that reside in and on the human body. These germs outnumber the body’s own cells 10 to 1, helping us break down food and overwhelm infectious germs. In exchange, we give them a nice place to live.
But when certain bacteria are allowed to proliferate, upsetting the internal ecosystem, health problems may develop. Changes in gut bacteria may have a role in everything from obesity and circadian cycles to irritable bowel syndrome and multiple sclerosis, research suggests.
Littman’s team of scientists was the first to show in humans that disturbances in the digestive tract may play a role in autoimmune attacks on the joints, according to 2013 research published in the open-access journal eLife.
Using a sophisticated DNA analysis technique, the scientists compared the gut bacteria from fecal samples of patients with rheumatoid arthritis with those of healthy people. They found a bacteria known as Prevotella copri was more abundant in patients with newly diagnosed rheumatoid arthritis than in healthy people or patients with chronic, treated rheumatoid arthritis.
Moreover, the overgrowth of P. copri was associated with fewer beneficial gut bacteria.
“There’s a lot of speculation about autoimmune diseases being associated with changes or disturbances in the microbiota,” Littman said. He called his team’s study results “the clearest association with a particular microbe to date.”
Still, while the connections have been made in animal models, more research needs to be completed in humans. Scientists first need to figure out whether the microbes are a cause or a consequence of the disease, said Yasmine Belkaid, senior investigator and chief of the Laboratory of Parasitic Diseases’ Mucosal Immunology Section at the National Institute of Allergy and Infectious Diseases.
Then scientists may need to develop “ways to selectively remove one microbe in a complex microbiota,” she said.
Moreover, even if certain bacteria can trigger the disease, “we also don’t know whether that is something that can be treated once the disease is out of the gate,” Littman said.
An estimated 1.3 million Americans have rheumatoid arthritis, in which the immune system attacks tissues, inflaming joints and damaging organs.
The condition is known to have a strong genetic component. But not all patients carry the genes, so environmental factors — smoking, hormones, aging and infections — must be involved too, said researcher Veena Taneja, an associate professor of immunology at the Mayo Clinic.
“The gut seems to be the common link,” said Taneja, whose work looks at whether bacteria can be manipulated to change the course of disease. “The gut microbiome is influenced by the genes and exposed to these things every day.”
The relationship between bacteria and the immune system begins at birth as the baby passes through the birth canal, collecting microbes that will colonize its body. As the child’s environment and food habits change, so do the bacteria.
“If there is immune system dysfunction, there can be an imbalance that results in disease and in inflammation,” Littman said.
Dysbiosis, or the abundance of certain bacteria because of factors such as antibiotics, stress and diet, can change the profile and trigger inflammation, Taneja said. If so-called unfriendly bacteria outnumber good bacteria, “it leads the body to produce a lot more of the pro-inflammatory cytokines,” or substances secreted by cells of the immune system, she said. “We’ve shown in mouse models that the presence of certain bacteria is associated with the pro-inflammatory status of the gut.”
According to one theory, if there is an imbalance in good and bad bacteria, metabolites are also unbalanced, Taneja said. This can cause a leaky gut, allowing for various metabolite or bacterial products to move outside the gut into the body. “Outside of the gut, these bacterial products may be seen as foreign, and the body starts to make an immune response to them,” she said.
It’s possible to change the type of bugs in the digestive tract by altering diet and using antibiotics, “but not in a way we can control very well,” Littman said. One day, scientists hope to develop pills containing particular microbes “that will establish themselves and change the composition of the microbiota from one that may make someone prone to disease to one that is beneficial,” he said.
For now, the best way to alter gut flora seems to involve permanent dietary and lifestyle changes. New York chef Seamus Mullen, 40, was diagnosed with rheumatoid arthritis in 2007 after living with symptoms for several years. He tried the usual treatments, starting with anti-inflammatory drugs, biologics and steroids, with no luck. Finally, he saw a doctor who suspected his arthritis was driven by an imbalance in his microbiome because of an infection.
Mullen said he followed a strict yearlong protocol, one that involved more exercise, more rest and the elimination of refined sugars and grains. He ate more fermented foods, which are naturally high in probiotics, took supplements and low-level antibiotics and avoided meat and poultry unless they came from grass-fed animals. Mullen also used acupuncture and diligently monitored how he was feeling.
After nine months, his blood values had returned to normal for the first time in a decade, and his arthritic symptoms had receded, he said. Though he realizes his case is anecdotal, he’s convinced “there’s a direct correlation between the foods we eat and the spectrum of bacteria in our guts,” he said.
Food “is a fundamental part of the journey,” Mullen said. “It’s not enough to say, ‘Oh, I’ll have some ginger today and some greens tomorrow,’ and expect a turnaround in your health.
“To really see change, it requires a wholesale reboot of how you live your life. Compliance isn’t easy, but it’s a small price to pay.”
