Pro-Biotic: engineered for Crohn Disease

BIOMEDICINE

Genetically Engineered Probiotics

A twist on a traditional therapy shows promise for treating bowel disease.

• TUESDAY, FEBRUARY 1, 2011
• BY EMILY SINGER

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Public interest in probiotics  is on the upswing, if the glut of advertisements for probiotic yogurts—those with added doses of beneficial bacteria—is any evidence. Scientists are bringing this traditional therapy into the 21st century by genetically engineering the microbes to enhance their effect on the immune system. They hope the new bugs will ultimately help treat inflammatory bowel diseases such as Crohn's disease and ulcerative colitis, as well as other disorders that result from an overactive immune system.

In research published today in the Proceedings of the National Academy of Sciences, scientists deleted a gene from the bacterium Lactobacillus acidophilus, which is commonly found in yogurt. Mansour Mohamadzadeh, associate professor of medicine at Northwestern University, and collaborators had previously shown that the enzyme this gene manufactures increases inflammation, a defining characteristic of Crohn's disease and ulcerative colitis. But the unaltered form of the bacterium also triggered production of a beneficial immune molecule, IL-10m, which helps to regulate the immune system. The goal of the engineering the microbes was to deliver the beneficial effects without the harmful ones.

When fed to mice with colitis and inflammation of the colon, the engineered bacteria prevented the weight loss and bloody diarrhea that typically accompanies this condition. In addition, the treated mice had 90 percent less inflammation in their colon tissue than did their untreated counterparts.

While probiotic foods and supplements are a huge industry, it's unclear whether they actually help treat most gastrointestinal diseases. The research published today is part of a trend in microbiology to explore in rigorous detail the effects of probiotics and the mechanisms that underlie them.

"The concept [of probiotics] is wonderful, but the evidence of their [effectiveness] is fairly limited," says Balfour Sartor, co-director of the Center for Gastrointestinal Biology and Disease at the University of North Carolina, who was not involved in the new study. Because probiotics are considered a food and not a drug, they are not regulated by the U.S. Food and Drug Administration, and therefore don't require the large clinical tests that drugs do.

Inflammatory bowel disease is one of the prime areas of interest for probiotic treatment, but "there really has been little direct evidence that probiotics are effective in treatment or prevention of Crohn's disease," says Sartor. Some research suggests that two different probiotic formulations can help prevent recurrence of ulcerative colitis, he says. "But that's just two out of thousands of formulations."

Scientists still don't know exactly how probiotic bacteria influence the gastrointestinal system, but previous research suggests several possible mechanisms. Beneficial bacteria might temporarily alter the ratio of good to bad bacteria that inhabit the intestine, or they might specifically block activity of bad bacteria. And probiotics seem to influence the immune system, "stimulating protective immune cells or blocking detrimental activities of immune cells," says Sartor.