Gut feeling

Probiotic microbe kicks on an anti-inflammatory process in mice

We are all crawling with bacteria, and researchers hope someday to induce some of these microbes within us to produce compounds that will fight disease. In a first step toward this goal, a team has identified a bacterial product that kicks on anti-inflammatory machinery in the intestines of mice and suppresses a condition similar to human Crohn’s disease.

The findings offer the first example of a microbe-generated compound that “networks” with the immune system to quell inflammation in a mammal, the scientists report in the May 29 Nature.

The human intestines house 300 to 1,000 distinct kinds of bacteria — some good and some bad. Many have never been clearly identified or even accurately counted. Their roles are also gradually being discerned to include more than food digestion.

But from an evolutionarily perspective, it’s a safe assumption that humans would have purged these bacteria long ago if the microbes had no purpose or were strictly detrimental, says Marika Kullberg, an immunologist at the University of York in England.

Since incidence of inflammatory bowel ailments such as Crohn’s disease have risen sharply in the West since the 1950s, identifying which gut bacteria have anti-inflammatory roles could be a boon to medicine.

With that in mind, physician and microbiologist Dennis Kasper of HarvardMedicalSchool in Boston and his colleagues tested mice that were bred to lack intestinal microbes. Using this living blank slate, the researchers induced inflammation in the animals’ colons and simultaneously fed the mice a microbe called Bacteroides fragilis. Earlier work had suggested that this bug has anti-inflammatory properties.

Introducing B. fragilis prevented inflammation. Further tests reveled that the bacterium produces a sugar called polysaccharide A, which induces immune cells to crank out an anti-inflammatory protein called interleukin-10. Feeding the sugar directly to the mice also inhibited inflammation in the animals, the researchers report.

Whether these results will translate to people is another matter, Kasper says, since interleukin-10 has a short half-life in people.

Nevertheless, studies like this “are pieces of the puzzle,” says Kullberg, who wasn’t involved in the research. “With more pieces, you get a better overview of how the system works.”

Inflammatory bowel diseases might result from an inappropriate immune attack on microbes — good and bad — in the gut, says Kullberg. Improved sanitation, a lifetime of antibiotic use and even vaccines against bacteria may disrupt the microbial equilibrium people have evolved to harbor in the gut, she says. In essence, some beneficial microbes may die from friendly fire.

How this disruption might translate into chronic inflammation remains unclear, she says. The cause of Crohn’s disease and other inflammatory bowel disorders probably includes genetic predisposition and maybe other factors, she says.

To sort out the mysteries of these gut flora, the National Institutes of Health is sponsoring the Human Microbiome Project, which seeks to identify the microbes that live within people and those microbes’ uses.

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