Casein Hydrolysate Enhances Upper Gastrointestinal Chemosensing and Gastric Acid Secretion in Pigs

Gastric chemosensing and gastric acid secretion affect nutrient utilization. Dietary peptides influence intestinal amino acid utilization, yet their regulation of gastric chemosensing and gastric acid secretion remains unknown. Herein, a pig model was employed to study the gastric response to dietary peptide-enriched casein hydrolysate versus intact casein. A total of 16 crossbred pigs (Duroc × Landrace × Yorkshire; 19.09 ± 0.61 kg; 63 ± 2 days of age) were randomly assigned to either an intact casein supplementation diet (<i>n</i> = 8) or a hydrolyzed casein supplementation diet (<i>n</i> = 8) for 28 days. Results showed that casein hydrolysate increased hydrochloric acid concentrations, parietal cell numbers, and H⁺-K⁺-ATPase activities in the stomach. Gastric chemosensing was upregulated, as indicated by the increased expression of peptide and amino acid chemosensors (G Protein-Coupled Receptor 92 and Calcium-Sensing Receptor) in the dorsum of the tongue, gastric corpus, and antrum. Signaling pathways involved in gastric acid secretion were also enhanced by casein hydrolysate, including extracellular stimuli (histamine, gastrin, and acetylcholine), their receptors, and intracellular signaling molecules. The upregulated gastric acid secretion was accompanied by lower amino acid concentrations in the gastric digesta and increased pepsin activity. These results demonstrate that casein hydrolysate enhances gastric chemosensing and gastric acid secretion, providing a promising nutritional strategy for regulating amino acid digestion.