Goat colostrum alleviates constipation through modulation of gut microbiota, microbial metabolism, and gastrointestinal regulators: Integrated in vitro and in vivo evidence.

Chronic constipation poses a global health burden, yet long-term pharmacological treatments are often limited by adverse effects, driving the demand for safe, diet-based nutritional strategies. While gut microbiota dysbiosis is central to constipation pathogenesis, the potential of goat colostrum to modulate this microecology remains underexplored. To bridge this gap, this study employed an integrated in vitro-in vivo approach to elucidate the systemic anti-constipation mechanisms of goat colostrum. Following simulated digestion, colostrum hydrolysate significantly reshaped the gut microbiota during fecal fermentation, enriching Bifidobacterium and Lactobacillus and increasing short chain fatty acids (SCFAs) production. In vivo, goat colostrum alleviated loperamide induced constipation in mice, accelerating intestinal transit, improving colonic mucosa, and modulating gastrointestinal regulators (motilin, 5-hydroxytryptamine, vasoactive intestinal peptide, and endothelin-1). Furthermore, peptidomics and molecular docking identified two core peptides from goat colostrum hydrolysate (AAPLLPNLGFG and AALPLPNLGFGM) with predicted interactions with coagulation factor II and cathepsin B (CTSB). SPR analysis showed measurable CTSB binding by AALPLPNLGFGM, and the enzyme assay indicated reduced CTSB-mediated substrate hydrolysis, whereas AAPLLPNLGFG showed no clear specific CTSB binding. Collectively, these findings suggest that goat colostrum alleviates constipation through a dual mechanism involving microbiota-SCFA-gastrointestinal regulator modulation and peptide-associated host-target effects. These findings highlight the significant potential of goat colostrum as an effective, natural functional food for managing chronic constipation and restoring intestinal homeostasis.