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Gut bacteria might trigger an autoimmune disease that can destroy vision.

Gut bacteria might trigger an autoimmune disease that can destroy vision.


Gut microbes linked to eye disease

Some microbes that naturally dwell in our intestines might be bad for our eyes, triggering autoimmune uveitis, one of the leading causes of blindness. A new study suggests that certain gut residents produce proteins that enable destructive immune cells to enter the eyes.

The idea that gut microbes might promote autoimmune uveitis “has been there in the back of our minds,” says ocular immunologist Andrew Taylor of the Boston University School of Medicine, who wasn’t connected to the research. “This is the first time that it’s been shown that the gut flora seems to be part of the process.”

As many as 400,000 people in the United States have autoimmune uveitis, in which T cells—the commanders of the immune system—invade the eye and damage its middle layer. All T cells are triggered by specific molecules called antigens, and for T cells that cause autoimmune uveitis, certain eye proteins are the antigens. Even healthy people carry these T cells, yet they don't usually swarm the eyes and unleash the disease. That's because they first have to be triggered by their matching antigen. However, those proteins don't normally leave the eye. So what could stimulate the T cells? One possible explanation is microbes in the gut.

In the new study, immunologist Rachel Caspi of the National Eye Institute in Bethesda, Maryland, and colleagues genetically engineered mice so their T cells recognized one of the same eye proteins targeted in autoimmune uveitis. The rodents developed the disease around the time they were weaned. But dosing the animals with four antibiotics that killed off most of their gut microbes delayed the onset and reduced the severity of the disease. The researchers saw the same effects in so-called germ-free mice, which lack gut bacteria.

To test whether gut microbes were stimulating these T cells, Caspi and colleagues added the intestinal contents of the diseased mice to T cell cultures. This gut goop switched on the cells, priming them for eye infiltration. The team wondered whether a protein released by the intestinal microbes was triggering the T cells, so they then added a protein-destroying enzyme to the intestinal mixture. The T cell response was weaker, suggesting they were responding to a protein. In another experiment, the scientists injected T cells from the genetically altered mice into control mice that were not prone to autoimmune uveitis. If these T cells haven’t been exposed to intestinal material, they don’t cause uveitis. But 86% of the animals developed autoimmune uveitis if they received a large dose of T cells that had been exposed to intestinal contents of diseased mice, the researchers report online today in Immunity.

The results suggest that certain bacteria in the intestines produce proteins that closely resemble those in the eye—and can switch on some T cells in the intestines. “We can prove that activation is occurring in the gut,” Caspi says. The activated cells then presumably travel to the eyes, which they enter and start to destroy.

“It’s a very rigorous approach, and it really adds to our knowledge” about the origins of autoimmune uveitis, says ocular immunologist Russell Read of the University of Alabama, Birmingham, who was not involved in the study. One question researchers now need to answer is why we don’t all have these autoimmune reactions in our retinas, says ocular immunologist James Rosenbaum of the Oregon Health & Science University in Portland. It’s possible, he says, that only some people have the bacteria that stimulate the T cells or that certain genes could leave some individuals vulnerable to the disease.

Caspi and colleagues are still trying to find out which gut proteins the T cells recognize and which bacteria produce them. “I don’t want to suggest that popping an antibiotic pill or taking a probiotic is going to be a solution for the disease,” she says. But identifying these molecular mimics of the eye proteins, along with the bacteria that spawn them, could help researchers develop new ways to treat or prevent autoimmune uveitis.