Oligosaccharides from human milk influence growth-related characteristics of intestinally transformed and non-transformed intestinal cells
Oligosaccharides from human milk influence growth-related characteristics of intestinally transformed and non-transformed intestinal cells
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DOI：
10.1017/s0007114507824068
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发表时间：
2008-03-01
影响因子：
3.6
通讯作者：
Kunz, Clemens
中科院分区：
文献类型：
--
作者：
Kuntz, Sabine;Rudloff, Silvia;Kunz, Clemens
母乳低聚糖（HMO）被认为会影响母乳喂养婴儿肠道微生物群落的组成。我们研究了牛奶HMO组分或单个寡糖对转化的人肠细胞（HT-29和Caco-2）和胎儿来源的非转化小肠上皮隐窝细胞（人肠上皮细胞; HIEC）增殖、分化和凋亡的直接影响。在HT-29、Caco-2和HIEC细胞中，我们观察到中性和酸性HMO组分以剂量依赖性方式诱导的生长抑制。然而，细胞系之间的影响不同，即HT-29和Caco-2细胞比HIEC细胞更敏感。在HT-29中，除两种岩藻糖基乳糖外，所有16种中性和酸性寡糖对细胞生长均有抑制作用。关于HT-29和HIEC细胞的分化诱导，观察到中性和酸性HMO组分的阈值浓度为7.5 mg/ml。在个别寡糖，只有唾液酸乳糖诱导分化的HT-29和HIEC细胞，没有影响，也没有馏分，也没有个别寡糖被发现在Caco-2细胞。仅在HT-29和HIEC细胞中检测到中性寡糖的强烈凋亡诱导作用，但酸性组分未检测到。HMO显示通过两种不同的机制诱导肠细胞的生长抑制，通过诱导分化和/或通过影响细胞凋亡抑制细胞周期进程。由于消化和吸收过程的发育和成熟取决于分化，我们的实验表明，寡糖在体外有效地影响胃肠道发育的各个阶段。
Human milk oligosaccharides (HMO) are considered to influence the composition of the gut microflora in breastfed infants. We investigated direct effects of milk HMO fractions or individual oligosaccharides on proliferation, differentiation and apoptosis in transformed human intestinal cells (HT-29 and Caco-2) and non-transformed small intestinal epithelial crypt cells of fetal origin (human intestinal epithelial cells; HIEC). We observed growth inhibition induced by neutral and acidic HMO fractions in HT-29, Caco-2 and HIEC cells in a dose dependent manner. However, the effects varied between cell lines, i.e. HT-29 and Caco-2 cells were more sensitive than HIEC cells. In HT-29, all 16 individual neutral and acidic oligosaccharides except from the two fucosyllactoses had an inhibitory effect on cell growth. Regarding the induction of differentiation in HT-29 and HIEC cells a threshold concentration was observed at 7.5 mg/ml for neutral and acidic HMO fractions. Among individual oligosaccharides, only sialyllactoses induced differentiation in HT-29 and HIEC cells; no effect neither of fractions nor of individual oligosaccharides was found in Caco-2 cells. A strong induction of apoptosis was only detected in HT-29 and HIEC cells for neutral oligosaccharide but not for acidic fractions. HMO were shown to induce growth inhibition in intestinal cells through two different mechanisms, by suppressing cell cycle progression through induction of differentiation and/or by influencing apoptosis. As the development and maturation of digestive and absorptive processes depend on differentiation our experiments show that oligosaccharides are effective at influencing various stages in gastrointestinal development in vitro.