Milk phospholipids ameliorate mouse colitis associated with colonic goblet cell depletion via the Notch pathway

As natural emulsifiers used in food products, phospholipids have been gaining increasing attention, whereas their intestinal health impacts are still unclear. This work aims to investigate the effect of milk phospholipids (MP) on dextran sodium sulfate (DSS)-induced colitis of C57BL/6 mice, compared with soybean phospholipids (SP), as well as the related mechanism. We found that unlike SP, MP supplementation (25 mg per kg BW) had a unique beneficial effect on the 2.5% DSS induced colitis (p < 0.05) and ameliorated the injury status of goblet cells, indicated by the increased number (p < 0.05) and size (p < 0.05) of the goblet cells and more acid mucins and antimicrobial peptides (p < 0.05). Meanwhile, MP supplementation restored the over-activated Notch pathway through balancing the level of Notch pathway ligand Dll4 in the colon subepithelial layer (p < 0.05), thus leading to the increase in the Math1 expression (p < 0.05), and consequently enhanced goblet cell restitution (p < 0.05). Furthermore, MP induced more goblet cells in the colonoid and colonic myofibroblast co-culture system (p < 0.05), which highlighted the indispensable role of colonic myofibroblasts, as an intestinal stem cell niche factor, in the goblet cell modulation effect of MP. These findings indicated that phospholipids from milk instead of soybean attenuated the severity of DSS-induced mouse colitis and prevented the depletion of colonic goblet cells through balancing the over-activated Notch pathway mediated by colonic myofibroblasts.