January 17, 2011

Altering Intestinal Microbiome May Be Double-Edged Sword

The microbiome of a person is made up of the genetic elements of the microorganisms that reside mostly within our intestines and on our skin. The characteristics of a microbiome can indicate both a healthy and diseased area within the body.

In a report in the current edition of the Journal of the Federation of American Societies for Experimental Biology, researchers at Baylor College of Medicine studied how the absence of a molecule, toll-like receptor 2 (Tlr2), can positively and negatively affect the microbiome of the intestinal tract.

Ulcerative colitis, colon cancer

"Tlr2 plays a role in bacterial recognition, intestinal inflammation and obesity. There is some evidence for the role of Tlr2 in the form of chronic large intestinal disease (ulcerative colitis), and colon cancer," said Dr. Richard Kellermayer, assistant professor of pediatric gastroenterology at BCM and lead author on the study. "The dysfunction or lack of this molecule may be beneficial and hazardous at the same time."

They found that some aspects of the microbiome of Tlr2-deficient mice resembled that of lean animals and humans. However, other differences were also observed in the animals lacking Tlr2.

"The deficiency increased inflammation-associated changes in the intestinal microbiome, some of which are similar to what is found in ulcerative colitis," Kellermayer said.

He added that the intestinal gene expression involved in immune processes was significantly modified in the Tlr2-deficient mice resembling gene expression patterns found in inflammatory bowel diseases.

Communications must be kept in balance

"The findings of this study reveal the delicate communication between the intestinal microbiome and the genes of the host that must be kept in balance to prevent common human diseases," Kellermayer said. "The results may bring us closer to finding new targets for the treatment of common metabolic and gastrointestinal disorders."

Other BCM researchers involved in this work include Drs. Alan Harris, Alfred Balasa, Tiffany D. Schaible, Reka Szigeti, Zhijie Li, James Versalovic and C. Wayne Smith.

The study was funded by the Crohn's and Colitis Foundation of America-Children's Digestive Health and Nutrition Foundation, the Broad Medical Research Program, the Broad Foundation, a USDA/ARS CHRC, CRIS Project Grant, the National Institute of Diabetes, Digestive and Kidney Disease (NIDDK) and National Center for Complementary and Alternative Medicine.


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