Mass. General researchers provide evidence linking leaky gut to chronic inflammation

While most practitioners in integrative medicine are well aware of "leaky gut" and its affect on overall health, new research is bringing this awareness to the mainstream medical community, and providing hard evidence that could lead to improved treatment protocols and interventions.

With the help of genetically engineered mice, scientists at the Massachusetts General Hospital (MGH) are moving closer to establishing the role that increased intestinal permeability, or leaky gut, plays in chronic inflammatory conditions, according to an April 20 press release.

Regulated by a protein called zonulin, elevated intestinal permeability has been associated with several chronic conditions including autoimmunity, metabolic disorders, neurodegenerative diseases, and cancer.

In an article published in Annals of the New York Academy of Sciences, lead author Craig Sturgeon, a graduate student in the Mucosal Immunology and Biology Research Center (MIBRC) at MGH, and colleagues provide a direct link between increased permeability of the small intestine and chronic inflammatory disease. They describe how inducing colitis in transgenic mice with two copies of the zonulin-producing gene variant led to significantly more severe symptoms and increased mortality compared with inducing colitis in animals without the zonulin gene.

"This is the first time that we have been able to mechanistically link zonulin-dependent modulation of small-intestinal permeability and the resulting enhanced antigen trafficking to the development of an inflammatory disease," says Alessio Fasano, MD, director of the MIBRC and senior author of the article. "When we exposed these two groups of mice to inflammatory stress, the zonulin transgenic mice showed a remarkable increase in colon inflammation and in mortality—up to 70 percent—compared to normal mice."

A professor of Pediatrics at Harvard Medical School, Fasano explains that, while some practitioners use the term "leaky gut syndrome" to describe a variety of health problems ranging from gastrointestinal complaints to neurological symptoms, he prefers the concept of "loss of intestinal barrier function."

"With the development of this mouse model to study inflammation, we'll be able to separate science from speculation," he says.