Pepsin and Its Importance for Functional Dyspepsia: Relic, Regulator or Remedy?

BACKGROUND: Functional dyspepsia is a heterogeneous disorder lacking an established therapeutic strategy. Historical treatment attempts with pepsin products were shrugged off, as a simple calculation shows that quantitative substitution is pointless. However, such attempts might have been right for the wrong reason.

SUMMARY: Today, the role of pepsins is primarily seen in the provision of signalling amino acids (especially phenylalanine and tryptophan) and peptides, which initiate processes promoting digestion. Proteolysis benefits from pepsin variants showing, contrary to common belief, activities of up to a pH value of 5.0. Non-clinical and clinical studies support the view that liberated amino acids produce a variety of direct and indirect effects. Signal chains stimulated by (mostly aromatic) amino acids lead to secretion of gastrin and cholecystokinin (CCK), mediated, respectively, by CCK2 (gastrin) and Ca2+-sensing receptors in the parietal cell, and Ca2+-sensing receptors in the antral and duodenal mucosa. Thus, CCK effects such as secretion of pancreatic enzymes and promotion of gastric accommodation are (also) consequential to peptic liberation of amino acids. Key Message: As functional dyspepsia represents a heterogeneous disorder, it may be intriguing to view pepsin as a potential (although still to be proven) treatment modality, distinguished by a diversity of pro-digestive effects.