Combination of galacto-oligosaccharides and wheat peptides synergistically relieved constipation via regulating water transport, gut barrier, inflammation and gut microbiota

Constipation is a common gastrointestinal problem. This study aimed to identify a combination of prebiotics and wheat peptides (WP) to promote intestinal peristalsis and explore the underlying mechanism. First, we screened four prebiotics (galacto-oligosaccharides (GOS), fructose oligosaccharides (FOS), inulin (IN), and resistant dextrin (RD)) using a zebrafish model and found that GOS was the most synergistic with WP. We then tested the GOS-WP combination in a mouse model of loperamide (Lop)-induced constipation and found that it significantly improved constipation symptoms. Specifically, GOS-WP shortened the first black stool time, increased the number of defecation particles, accelerated small intestinal propulsion rate, and increased fecal water content. GOS-WP also normalized the colonic water transport system by inhibiting colonic AQP4/8 expression. Additionally, GOS-WP reversed Lop-induced morphological damage in the ileum and colon, increased colonic barrier, and reduced inflammation in mice. Furthermore, 16S rRNA gene sequence analysis showed that GOS-WP reversed the gut microbiota structure changes induced by Lop. GOS-WP significantly increased butyric acid and decreased BCFA levels, indicating improved gut health. Our findings suggest that the GOS-WP combination has potential as a novel intervention for constipation relief. This study highlights the potential of combining prebiotics and WP as a therapeutic strategy for constipation.