The human protein elafin could be delivered into the gut using a probiotic bacterium to reduce the inflammatory reaction typical of celiac disease, researchers suggest.
The patent-pending strategy has been developed by teams at the French National Institute for Agricultural Research (INRA) and the French National Institute of Health and Medical Research (INSERM) along with Canadian and Swiss colleagues.
Published online in the American Journal of Gastroenterology today (April 8), scientists delivered the elafin molecule using a food-grade strain of L. lactis successfully in mice for the first time.
INRA said findings opened up “promising prospects to treat celiac disease and gluten intolerance in general”.
The researchers said: “This molecule may have pathophysiological and therapeutic importance in gluten-related disorders.”
Elafin and its role in the gut
In the same study, in vitro testing found that elafin, a protease inhibitor, played a key role in fighting against inflammatory reactions in the gut that were typical of celiac disease, ultimately reducing gluten toxicity.
The protein prevented the destruction of the gut barrier during inflammation and interacted with enzymes responsible for the abnormal breakdown of gluten: transglutaminase-2, the researchers said.
“Our in vitro results point at an exciting novel role and specific mechanism of action of elafin in celiac disease that should be further explored.”
However, they found that the protein was less abundant in patients with celiac disease compared to healthy people; a loss that could be contributing to enhanced inflammation in celiac disease.
Delivery with a lactic bacterium strain
The lack of natural elafin molecules in those with celiac disease prompted the researchers to investigate methods of delivery. The scientists successfully delivered the protein to mice using a lactic bacterium strain Lactococcus lactis.
Findings showed that elafin delivery at the mucosal level prevented gluten-induced barrier dysfunction and inflammation.
“The use of this strain, developed by the same teams from INRA and INSERM, enables a targeted and local production of elafin, and represents a recent and innovative strategy,” INRA said.
The researchers said replacement of elafin molecules in celiac patients could have potential as adjuvant therapy in gluten-related disorders but said it was important to investigate details further.
The next step, they said, would be to define the mechanisms underlying the positive effects of elafin in celiac disease and identifying bacteria that naturally produce proteins with anti-inflammatory properties similar to elafin.
Source: American Journal of Gastroenterology
Published online ahead of print, April 8 2014. Doi: 10.1038/ajg.2014.48
“Novel Role of the Serine Protease Inhibitor Elafin in Gluten-Related Disorders”
Authors: HJ. Galipeau et al.
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