Stratingh Institute for Chemistry, University of Groningen, Groningen, the Netherlands.
Department of Pathology and Medical Biology, University Medical Center Groningen, Groningen, the Netherlands.
Food Funct. 2021 Jun 8;12(11):5018-5026. doi: 10.1039/d1fo00830g.
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-β-cyclodextrin (DFβCD), which was inspired by the molecular structures of hMOs. We establish that DFβCD is not digested by α-amylase and also resistant to fermentation by microbial enzymes from a 9 month-old infant inoculum. In addition, we reveal that DFβCD blocks adhesion of enterotoxigenic E. coli (ETEC) to Caco-2 cells, especially when DFβCD is pre-incubated with ETEC prior to addition to the Caco-2 cells. This suggests that DFβCD 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.
人乳被广泛认为是婴儿的最佳食物，这不仅仅是因为其营养成分。人乳还含有大量生物活性分子，包括一大组人乳低聚糖（hMOs）。特别是岩藻糖基 hMOs 因其对病原体的抗粘附作用而受到关注，可防止其附着在肠道上并感染。由于 hMOs 通常难以大量生产以进行研究并最终应用于（医学）婴儿配方奶粉中，因此受 hMO 结构启发的新型化合物（所谓的“模拟物”）是很有前途的生产和评估其生物效应的化合物。在这里，我们对受 hMO 分子结构启发的新型化合物二岩藻糖基-β-环糊精（DFβCD）的消化、发酵和抗粘附能力进行了深入研究。我们确定 α-淀粉酶不能消化 DFβCD，并且它也能抵抗来自 9 个月大婴儿接种物的微生物酶的发酵。此外，我们揭示了 DFβCD 可以阻止肠产毒性大肠杆菌（ETEC）与 Caco-2 细胞的粘附，尤其是当 DFβCD 在添加到 Caco-2 细胞之前与 ETEC 预孵育时。这表明 DFβCD 通过诱饵效应发挥作用。我们期望我们的结果能够激发其他岩藻糖基 hMOs 和模拟物的生成和生物学评估，以全面了解岩藻糖基聚糖的抗粘附能力。
