Despite multiple associations between the microbiota and immune diseases, their role in autoimmunity is poorly understood. We found that translocation of a gut pathobiont, Enterococcus gallinarum, to the liver and other systemic tissues triggers autoimmune responses in a genetic background predisposing to autoimmunity. Antibiotic treatment prevented mortality in this model, suppressed growth of E. gallinarum in tissues, and eliminated pathogenic autoantibodies and T cells. Hepatocyte–E. gallinarum cocultures induced autoimmune-promoting factors. Pathobiont translocation in monocolonized and autoimmune-prone mice induced autoantibodies and caused mortality, which could be prevented by an intramuscular vaccine targeting the pathobiont. E. gallinarum–specific DNA was recovered from liver biopsies of autoimmune patients, and cocultures with human hepatocytes replicated the murine findings; hence, similar processes apparently occur in susceptible humans. These discoveries show that a gut pathobiont can translocate and promote autoimmunity in genetically predisposed hosts.
Researchers at Yale University in New Haven, CT, have discovered that intestinal bacteria in mice and humans can travel to other organs and evoke autoimmune response. But, administering antibiotic or vaccine that targets the bacteria can subdue this autoimmune reaction.
In autoimmune diseases, our immune system which is supposed to protect us turns on us and starts attacking our healthy cells and tissues. As a result, our body’s ability to fight off foreign invaders decreases, making us susceptible to range of infections. Some of the most common autoimmune diseases are rheumatoid arthritis, inflammatory bowel disease (IBD), psoriasis and type 1 diabetes.
Scientists have not fully understood the cause of autoimmune diseases, but they have long suspected bacteria in the gut to be the culprit as a variety of autoimmune conditions have been linked to it.
In the study, senior author Martin Kriegel, M.D. and his team centered on a gut bacteria called Enterococcus gallinarum, which can “translocate” to lymph nodes, the liver, and spleen. Using a genetically susceptible mouse model, they were able to observe that once traveled beyond the gut, E. gallinarum triggered autoimmune responses and initiated producing auto-antibodies and inflammation.
Researchers were able to substantiate the same mechanism of inflammation in cultured liver cells of healthy people. They also found E. gallinarum to be present in livers of patients with autoimmune disease.
Further experiments showed that autoimmunity in the mice can be suppressed with an antibiotic or a vaccine designed to target E. Gallinarum. Either of the approach inhibited the growth of the bacterium in the tissues and alleviated its effects on the immune system.
“When we blocked the pathway leading to inflammation, we could reverse the effect of this bug on autoimmunity,” Martin Kriegel, M.D. explained. “The vaccine against E. gallinarum was a specific approach, as vaccinations against other bacteria we investigated did not prevent mortality and autoimmunity.”
The findings were published in the journal Science. Researchers believe treatment of chronic autoimmune conditions, including systemic lupus and autoimmune liver disease, can be made easy with further research on E. gallinarum and its mechanisms.