Dust mite allergen a possible player in intestinal disease

Reuters Health Information: Dust mite allergen a possible player in intestinal disease

Dust mite allergen a possible player in intestinal disease

Last Updated: 2016-01-25

By Anne Harding

NEW YORK (Reuters Health) - House dust mite (HDM) allergen promotes inflammation and gut permeability in humans, according to new findings.

"We show a new possible player in the pathophysiology of inflammatory gut disease," Dr. Valerie Verhasselt of the University of Nice Sophia-Antipolis in Nice, France, told Reuters Health in a telephone interview. The findings were published online December 8 in Gut.

HDM is the main cause of asthma and other allergic respiratory disease. The main antigen from the common dust mite Dermatophagoides pteronyssinus, the cysteine protease Der p1, has been shown to weaken tight junction (TJ) proteins in the respiratory epithelium, Dr. Verhasselt and her colleagues noted.

A similar breakdown in the human gastrointestinal tract epithelium has been found in inflammatory bowel disease (IBD) and inflammatory bowel syndrome (IBS), they added, but the triggers for this breakdown are unclear.

To investigate whether Der p1 is present in the human gut and how it might affect gut barrier function, the researchers examined biopsies, gut fluid, serum, and stool from healthy controls and IBS patients undergoing endoscopy.

They found Der p1 in 13 out of 28 diluted duodenal fluid samples from the healthy individuals, and in all stool samples from healthy volunteers. Adding HDM to biopsies of healthy gut tissue increased epithelial permeability, and also promoted production of tumor necrosis alpha and interleukin 10. HDM also disrupted epithelial TJ proteins, while cysteine protease inhibitor prevented HDM-induced inflammation and epithelial breakdown. Experiments in mice confirmed that HDM had a protease-dependent effect on colon permeability, and also revealed that HDM exposure weakened the mucus layer in the colon.

The effects of HDM were independent of Th2, and were stronger in individuals with IBS compared to the healthy controls.

"You don't need to be allergic to react to house dust mite in your gut," Dr. Verhasselt said. However, she added, "if you are susceptible and already have some ongoing gut disease, you react more strongly to HDM than healthy people, and importantly you have a weaker counter-regulatory response."

Given the ubiquity of HDM exposure, Dr. Verhasselt added, "It's probably very difficult to avoid." But the findings do point toward treatment strategies, she said, including identifying the counter-regulatory mechanisms in the guts of healthy individuals and finding ways to induce these mechanisms in people with inflammatory gut disease. Another approach, she added, would be to blunt Der p1's inflammatory effects with cysteine protease inhibitors.

"This study is the first evidence for a role for house dust mite allergens in intestinal disease," Dr. Manon Wildenberg, of the Tygat Institute for Liver and Intestinal Research at Academic Medical Center in Amsterdam, the Netherlands, told Reuters Health by email. "These allergens were previously only considered in pulmonary disease, but now prove to have broader effects."

Dr. Wildenberg co-authored an editorial accompanying the new study. "The data suggests that the proteolytic properties rather than the allergenic properties of HDM are responsible for the effect in the intestine," she said. "This would suggest that a clinical application of these findings should be aimed at inhibiting proteolysis and not at preventing immune responses (which is the case in asthma). However, this is a first step, and much more research will be required before this will translate into clinical practice."

"This study shows that a common cause such as HDM can be involved in several medical conditions, but through different effector mechanisms," Dr. Wildenberg added. "Due to the difference in effector mechanisms, treatments aimed at eradicating the cause in one disease may not be effective in another disease. This lack of efficacy should therefore not be regarded as proof for lack of involvement of the cause, but only as proof of differences in pathological mechanisms."

Multiple organizations supported this research. The authors reported no disclosures.

SOURCE: http://bit.ly/1njnFLu and http://bit.ly/1PfP7om

Gut 2015.

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