Wheat peptides alleviate constipation by promoting enteric neurogenesis via mAChR-mediated calcium signaling pathways in mice

Constipation is a prevalent gastrointestinal issue. Wheat peptides (WP) effectively alleviate loperamide-induced constipation in mice. Oral administration of WP (0.5 mg/g.bw) improved defecation, small intestinal propulsion, and intestinal barrier function in mice. WP also modulated gut inflammation and enteric nervous system factors. Additionally, WP intervention effectively rectified gut microbiota dysbiosis by restoring microbial diversity and modulating gut bacteria to approach normal levels. Of particular significance, transcriptome data indicated alterations in gene expressions related to the calcium signaling pathway in the colon of constipated mice. RT-qPCR analysis further corroborated that WP upregulated the gene expression of cholinergic receptor ( Chrm1 ), Itpr2 / 3 , Calml3 , and Calm 4 . Furthermore, 3D microscopy revealed that WP increased the number of enteric nerves in the colon of constipated mice. These findings suggest WP mitigate constipation by activating muscarinic acetylcholine receptors, enhancing calcium signaling, and promoting enteric neurogenesis to improve intestinal peristalsis. Overall, WP demonstrate therapeutic potential for treating constipation.