Could a bacterium found in milk trigger rheumatoid arthritis?

New research suggests that a bacterium found in cow’s milk and beef may lead to rheumatoid arthritis in people who are already genetically predisposed. The bacterium may be a common trigger for both rheumatoid arthritis and Crohn’s disease.

A bacterium found in milk may trigger rheumatoid arthritis in genetically predisposed people, suggests new research.

Rheumatoid arthritis is an inflammatory disease that affects more than 1.3 million adults — the majority of whom are women — in the United States.

Crohn’s disease is also an inflammatory disease, and the Crohn’s and Colitis Foundation say that it affects up to 780,000 U.S. adults.

What do these two diseases have in common, apart from being characterized by inflammation? Quite a lot, actually, according to new researchrecently published in the journal Frontiers in Cellular and Infection Microbiology.

Both of these conditions share a similar genetic background and are often treated with similar immunosuppressants, because both illnesses are autoimmune disorders.

These similarities intrigued the authors of the new research, who are: Saleh Naser, who is an infectious disease specialist at the University of Central Florida (UCF) in Orlando; Dr. Shazia Bég, who is a rheumatologist at UCF’s physician practice; and Robert Sharp, who is a Ph.D. candidate in biomedical sciences at UCF’s medical school.

“Here,” says Naser, “you have two inflammatory diseases, one affects the intestine and the other affects the joints, and both share the same genetic defect and [are] treated with the same drugs. Do they have a common trigger? That was the question we raised and set out to investigate.”

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In previous research, Naser had already discovered a link between the bacterium Mycobacterium avium subspecies paratuberculosis (MAP) and Crohn’s disease, so the question of whether MAP was also somehow connected with rheumatoid arthritis followed naturally.

In fact, Naser is currently involved in a clinical trial investigating whether or not Crohn’s disease can be treated with antibiotics. Thus, if MAP proves to be present in rheumatoid arthritis as well, this condition may also be treatable with antibiotics designed to specifically target this bacterium.

Gene mutation plus MAP means higher risk

The researchers analyzed clinical samples from 100 people with rheumatoid arthritis. Of these, 78 percent had a genetic mutation that they shared with people with Crohn’s disease: the PTPN2/22 gene.

Of the people with rheumatoid arthritis with this genetic mutation, 40 percent also had MAP.

“We believe that individuals born with this genetic mutation and who are later exposed to MAP through consuming contaminated milk or meat from infected cattle are at a higher risk of developing rheumatoid arthritis.”

“We don’t know the cause of rheumatoid arthritis, so we’re excited that we have found this association,” Bég says. “But there is still a long way to go.”

Directions for future research

“We need to find out,” say the authors, “why MAP is more predominant in these patients — whether it’s present because they have RA [rheumatoid arthritis], or whether it caused RA in these patients. If we find that out, then we can target treatment toward the MAP bacteria.”

To this end, the researchers plan to carry out further studies, in the hope that their findings will be replicated.

National studies should now also investigate how many patients get both rheumatoid arthritis and Crohn’s disease, say the scientists. They themselves plan to examine the association further in people from different countries and of different ethnicities.

“Understanding the role of MAP in rheumatoid arthritis,” explains Naser, “means the disease could be treated more effectively. Ultimately, we may be able to administer a combined treatment to target both inflammation and bacterial infection.”

Crohn’s disease: Discovery of two subtypes could lead to better treatments

Crohn’s disease is notoriously difficult to treat due to the course and severity of the disease varying from one case to another. Research by University of North Carolina School of Medicine has discovered two subtypes of the disease – with different gene expressions and clinical features – which may reveal why such variations in disease progression surface between patients.

The discovery of two classes of Crohn’s has implications for scientists to deliver more targeted treatments.

Crohn’s disease – a long-term condition that causes inflammation to the lining of the digestive system – affects almost 1 million people in the United States. While there is no cure for Crohn’s, treatment with anti-inflammatory drugs and immune system suppressors can help improve symptoms.

Around 70 percent of people with Crohn’s will eventually require surgery to remove damaged portions of the digestive tract and reconnect to healthy sections, and as many as 39 percent will require repeated surgery. Surgery may also close fistulas and drain abscesses.

The study findings – published in the journal Gut – build upon existing knowledge of the biology of Crohn’s disease, and they could potentially lead to more effective strategies and personalized treatments to target the debilitating gastrointestinal condition.

“The one-treatment-fits-all approach doesn’t seem to be working for Crohn’s patients,” says co-senior study author Dr. Shehzad Z. Sheikh, Ph.D., assistant professor in University of North Carolina’s (UNC) departments of medicine and genetics.

“It’s plausible that this is because only a subset of patients has the type of disease that responds to standard therapy, whereas, for the rest of the patients, we’re really not hitting the right targets,” he adds.

Genes that varied between subtypes distinguish colon from ileum

With co-senior author Terry Furey, Ph.D., associate professor in UNC’s departments of genetics and biology, Sheikh and team analyzed colon tissue samples that looked healthy and non-inflamed in 21 Crohn’s patients who had undergone surgery. They then mapped levels of gene expression patterns amongst the samples, finding that there were two distinct groups.

“Although we saw a difference between the Crohn’s samples and samples from people without Crohn’s, we saw an even greater difference at the molecular level between these two subsets of the Crohn’s samples – the healthy tissue from Crohn’s patients and the inflamed samples from Crohn’s patients,” says Furey.

Co-first author Jeremy Simon, Ph.D., a research assistant professor in UNC’s department of genetics, notes that how the two disease subtypes differed was surprising.

Despite the samples being colon biopsies, Simon says, many of the genes that were varied between the two Crohn’s subtypes were markers that distinguish the colon from the ileum – the portion of the small intestine that empties into the colon and is usually the first area to be affected by Crohn’s disease.

The pattern of gene expression in one of the disease subtypes resembled healthy colon tissue. However, the gene expression in the second subtype resembled patterns seen in the ileum.

In addition to analyzing gene expression in the sampled tissue, Sheikh and colleagues observed indicators of the epigenetic state of the DNA tissue that can permit or repress nearby gene activity. The team saw a distinction between the two Crohn’s subtypes in the results that suggest the differences in gene expression emerge from variations in the core programming of the affected cells.

Crohn’s subtypes linked to two different clinical illness patterns

The researchers ensured that the fact that the samples were from adults who had undergone surgery did not skew the results, due to treatment and disease histories, by comparing their data to another dataset.

The team examined data from 201 children who had recently been diagnosed with Crohn’s and had not yet been treated. While the tissue samples in the data were from the ileum, the same colon-like and ileum-like disease classes were observed.

“This suggests that these molecular programs or baseline genomic signatures of Crohn’s subtypes exist independently of patients’ ages or treatment histories,” says Sheikh. He also points out that the two signatures are linked to different patterns of clinical illness.

For example, patients with the colon-like subtype were more likely to be characterized by gut inflammation found during colonoscopy, rectal disease, and colon inflammation severe enough to require colon removal.

In future work, Sheikh, Furey, and collaborators aim to develop a diagnostic test for use on tissue or blood samples taken from routine colonoscopies. By identifying which Crohn’s subtype a patient has, healthcare providers can determine the best therapy for treatment.