Crohn's treatment restores gut barrier

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Crohn's treatment restores gut barrier

Last Updated: 2002-09-24 12:01:34 -0400 (Reuters Health)

By Merritt McKinney

NEW YORK (Reuters Health) - New research confirms that Crohn's disease, a

chronic inflammatory bowel disease, causes the protective lining in the gut

to become more permeable than usual, which allows potentially harmful

substances to pass through it.

But blocking a protein called tumor necrosis factor (TNF) not only reduced

inflammation in the gut but also closed most of the holes in the gut

barrier.

" Our data confirm the central role of TNF in gut barrier modulation in

inflammatory conditions, " the study's first author, Dr. Suenaert of

the Catholic University Leuven in Belgium, told Reuters Health. The research

also " gives evidence for the view that gut barrier function and inflammation

are strongly interrelated, " he said.

The research, published in a recent issue of the American Journal of

Gastroenterology, answers some, but not all, questions about Crohn's

disease, according to the Belgian researcher. For the time being, Suenaert

said, the question of which comes first--a leaky gut or the inflammatory

reaction that triggers chronic inflammation--is still impossible to answer.

Crohn's disease is a type of inflammatory bowel disease with symptoms that

include pain, abdominal cramps, diarrhea, bleeding and weight loss. Drugs

and surgery to remove the portion of the intestine affected by the disease

may relieve symptoms, but there is no cure.

Suenaert explained that the small bowel and colon are lined by a single

layer of cells that not only absorbs nutrients but also protects against

outside invaders and harmful substances like bile acid. Together with other

cells in the intestine, this layer forms a barrier between the gut and the

bloodstream, he said.

Crohn's researchers have thought that the disease is caused by a defect in

the gut barrier that allows harmful substances to pass through it,

triggering an immune response that sets off chronic inflammation in the gut.

But it has been uncertain whether the leaky gut in Crohn's patients precedes

inflammation or is a consequence of it.

That remains a chicken and egg question, according to Suenaert, but a study

of 23 patients with Crohn's confirms that the protein TNF is involved in

both the inflammation and gut permeability that characterize Crohn's

disease.

In the study, patients were given a single infusion of infliximab, a Crohn's

drug that neutralizes TNF activity. The researchers evaluated inflammation

and the gut barrier before treatment and 4 weeks later.

Blocking TNF not only reduced inflammation but also largely restored the gut

barrier in Crohn's patients, the report indicates. The fact that blocking a

single protein restored the gut barrier and reduced inflammation suggests

that the inflammation and the function of the barrier are " closely

interrelated, " the researchers conclude.

SOURCE: American Journal of Gastroenterology 2002;97:2000-2004.