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Functional activity of histatins and other salivary proteins in the proteolytic context of whole saliva.
Research by Helmerhorst and coworkers is focusing on the role of the microbiome of the upper gastro-intestinal tract, the oral cavity, in the digestion of dietary gluten. Dietary gluten comprise a family of proteins that are abundantly present in the Western diet. Gluten proteins are fairly difficult to digest because of their unusual amino acid content and -sequence. In genetically predisposed individuals, gluten proteins elicit an auto-immune response leading to the destruction of the villi of the small intestine thus interfering with efficient uptake of nutrients causing celiac disease. The predominant amino acids in the gluten sequences are proline (Pro) and glutamine (Gln). Our recent investigations indicate that human saliva contains unique enzymes that can cleave the peptide bond C-terminal to the Xaa-Pro-Gln sequence. This tripeptide is prevalent in T-cell stimulatory gluten domains. While the human digestive enzyme system apparently lacks the capacity to neutralize essential immunogenic gluten domains implicated in celiac disease, such activities are naturally present in the oral microbial proteasome. These novel findings offer clinical insights as well as therapeutic perspectives for the treatment of celiac disease.
Functional activity of histatins and other salivary proteins in the proteolytic context of whole saliva.
Research by Helmerhorst and coworkers is focusing on the role of the microbiome of the upper gastro-intestinal tract, the oral cavity, in the digestion of dietary gluten. Dietary gluten comprise a family of proteins that are abundantly present in the Western diet. Gluten proteins are fairly difficult to digest because of their unusual amino acid content and -sequence. In genetically predisposed individuals, gluten proteins elicit an auto-immune response leading to the destruction of the villi of the small intestine thus interfering with efficient uptake of nutrients causing celiac disease. The predominant amino acids in the gluten sequences are proline (Pro) and glutamine (Gln). Our recent investigations indicate that human saliva contains unique enzymes that can cleave the peptide bond C-terminal to the Xaa-Pro-Gln sequence. This tripeptide is prevalent in T-cell stimulatory gluten domains. While the human digestive enzyme system apparently lacks the capacity to neutralize essential immunogenic gluten domains implicated in celiac disease, such activities are naturally present in the oral microbial proteasome. These novel findings offer clinical insights as well as therapeutic perspectives for the treatment of celiac disease.
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