Digestion, fermentation, and pathogen anti-adhesive properties of the hMO-mimic di-fucosyl-β-cyclodextrin

Human milk is widely acknowledged as the best food for infants, and that is not just because of nutritional features. Human milk also contains a plethora of bioactive molecules, including a large set of human milk oligosaccharides (hMOs). Especially fucosylated hMOs have received attention for their anti-adhesive effects on pathogens, preventing attachment to the intestine and infection. Because hMOs are generally challenging to produce in sufficient quantities to study and ultimately apply in (medical) infant formula, novel compounds that are inspired by hMO structures (so-called mimics) are interesting compounds to produce and evaluate for their biological effects. Here we present our thorough study into the digestion, fermentation and anti-adhesive capacity of the novel compound di-fucosyl-beta-cyclodextrin (DF beta CD), which was inspired by the molecular structures of hMOs. We establish that DF beta CD is not digested by alpha-amylase and also resistant to fermentation by microbial enzymes from a 9 month-old infant inoculum. In addition, we reveal that DF beta CD blocks adhesion of enterotoxigenic E. coli (ETEC) to Caco-2 cells, especially when DF beta CD is pre-incubated with ETEC prior to addition to the Caco-2 cells. This suggests that DF beta CD functions through a decoy effect. We expect that our results inspire the generation and biological evaluation of other fucosylated hMOs and mimics, to obtain a comprehensive overview of the anti-adhesive power of fucosylated glycans.

Automated summary

The novel compound di-fucosyl-beta-cyclodextrin (DF beta CD), inspired by the molecular structures of hMOs, shows potential in digestion, fermentation, and anti-adhesive capacity, particularly against certain pathogenic bacteria.