Common type of inflammatory bowel disease linked to toxic bacteria

The toxin produced by bacteria found in dirty water kills immune cells in the lining of the colon, meaning people whose intestines are colonized by these bacteria are much more likely to develop a disease known as ulcerative colitis.

This conclusion was reached by the results of a series of studies on humans and animals conducted by Xuena Zhang at Nanjing University in China and her colleagues. If confirmed, this finding could lead to new treatments for this disease.

Ulcerative colitis is one of two main types from inflammatory bowel diseaseor IBD. Characterized by inflammation of the mucous membrane of the colon and rectum. People usually have periods of no symptoms followed by flare-ups. In the most severe cases, the colon may need to be removed.

The causes of ulcerative colitis are unclear, but it is usually considered an autoimmune disease with complex environmental and genetic causes. Zhang and her team suggested that immune cells known as macrophages might play a role.

Macrophages are found in most tissues of the body, where they destroy debris and bacteria and also help regulate local immune responses. They can sound the alarm by triggering more immune cells, causing inflammation, but crucially, they can also sound the alarm by reducing inflammation.

In colon tissue taken from people with ulcerative colitis, researchers found lower levels resident macrophages than in people without the disease. They then showed that killing macrophages in the colons of mice made them more susceptible to colitis. Researchers believe that the loss of protection normally provided by macrophages leads to damage and inflammation of the colon lining.

But why were macrophage levels lower in people with ulcerative colitis? By testing fecal bacteria samples from people with the disease, the team found a toxin called aerolysinwhich appears to be highly damaging to macrophages but has little effect on other intestinal cells.

Aerolysin is produced by certain strains of bacteria. in the family Aeromonaswhich are commonly found in fresh and brackish waters. Researchers call the strains that produce aerolysin MTB (macrophagotoxic bacteria).

When the team deliberately infected mice with MTB, it made them more susceptible to colitis. But if the aerolysin gene was removed from the bacteria, or if the toxin was neutralized by antibodies, the mice did not become more susceptible to colitis.

Finally, the researchers looked for Aeromonas bacteria in stool samples. They found them in 72 percent of 79 people with ulcerative colitis, but only 12 percent of 480 people without the disease. This test was unable to determine whether these bacteria are MTB and therefore whether they produce aerolysin.

Overall, the research points to a complex picture. Not every case of ulcerative colitis can be associated with MTB, and people can also have MTB in the intestine without developing colitis.

“We cannot conclude that MTB is the sole cause of ulcerative colitis,” Zhang says. “Persistent MTB infection can cause a condition of colon hypersensitivity, but this does not mean that every infected person will develop colitis.

“The occurrence of colitis in this context is certainly influenced by environmental and genetic factors,” she says.

According to Zhang, there are at least three potential approaches to developing new treatments. One option would be to develop drugs that neutralize the toxin. It would be different develop vaccines affecting either the toxin or the bacteria that produce it. The third option is to use viruses that kill certain bacteriaknown as phage therapyto destroy bacteria that produce toxins.

“There is strong evidence that MTB toxin impairs intestinal immunity by depleting specialized macrophages in intestinal tissue,” says Martin Kriegel at the University Hospital Münster in Germany.

He notes that when the team eliminated all gut bacteria in the mice and then infected them with MTB, the animals did not become more susceptible to colitis. This suggests the presence of other, as yet unidentified bacteria. also play a role.

“However, it may represent an important missing factor in the multistep pathogenesis of ulcerative colitis, at least in China,” says Kriegel.

Zhang and her team now plan to conduct larger epidemiological studies to try to confirm the link between MTB and ulcerative colitis. If MTB infections do play a role and are becoming more common, this may help explain why the incidence of IBD is rising.