School of Food and Health, Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Engineering and Technology Research Center of Food Additives, Beijing Technology and Business University, Beijing 100048, China.
Department of Pathology and Medical Biology, University of Groningen and University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands.
Food Funct. 2021 Dec 13;12(24):12513-12525. doi: 10.1039/d1fo02563e.
Human milk oligosaccharides (hMOs) are unique bioactive components in human milk. 3-Fucosyllactose (3-FL) is an abundantly present hMO that can be produced in sufficient amounts to allow application in infant formula. Lacto--triaose II (LNT2) can be obtained by acid hydrolysis of lacto--neotetraose (LNnT). Both 3-FL and LNT2 have been shown to have health benefits, but their impact on infant microbiota composition and microbial metabolic products such as short-chain fatty acids (SCFAs) is unknown. To gain more insight in fermentability, we performed fermentation studies of 3-FL and LNT2 using pooled fecal microbiota from 12-week-old infants. The commonly investigated galacto-oligosaccharides (GOS)/inulin (9 : 1) served as control. Compared to GOS/inulin, we observed a delayed utilization of 3-FL, which was utilized at 60.3% after 36 h of fermentation, and induced the gradual production of acetic acid and lactic acid. 3-FL specifically enriched bacteria of and genus. LNT2 was fermented much faster. After 14 h of fermentation, 90.1% was already utilized, and production of acetic acid, succinic acid, lactic acid and butyric acid was observed. LNT2 specifically increased the abundance of , as well as The GOS present in the GOS/inulin mixture was completely fermented after 14 h, while for inulin, only low DP was rapidly utilized after 14 h. To determine whether the fermentation might lead to enhanced colonization of commensal bacteria to gut epithelial cells, we investigated adhesion of the commensal WCFS1 to Caco-2 cells. The fermentation digesta of LNT2 collected after 14 h, 24 h, and 36 h, and GOS/inulin after 24 h of fermentation significantly increased the adhesion of WCFS1 to Caco-2 cells, while 3-FL had no such effect. Our findings illustrate that fermentation of hMOs is very structure-dependent and different from the commonly applied GOS/inulin, which might lead to differential potencies to stimulate adhesion of commensal cells to gut epithelium and consequent microbial colonization. This knowledge might contribute to the design of tailored infant formulas containing specific hMO molecules to meet the need of infants during the transition from breastfeeding to formula.
人乳寡糖（hMOs）是母乳中独特的生物活性成分。3-岩藻糖基乳糖（3-FL）是一种大量存在的 hMO，其产量足以允许在婴儿配方奶粉中应用。乳-三糖 II（LNT2）可以通过酸水解乳-新四糖（LNnT）得到。3-FL 和 LNT2 都已被证明具有健康益处，但它们对婴儿微生物群组成和微生物代谢产物（如短链脂肪酸（SCFA））的影响尚不清楚。为了更深入地了解发酵性，我们使用来自 12 周龄婴儿的粪便微生物群进行了 3-FL 和 LNT2 的发酵研究。常用的半乳糖-低聚糖（GOS）/菊粉（9:1）作为对照。与 GOS/菊粉相比，我们观察到 3-FL 的利用延迟，在 36 小时的发酵后，其利用率为 60.3%，并诱导了乙酸和乳酸的逐渐产生。3-FL 特异性富集 属和 属的细菌。LNT2 发酵得更快。发酵 14 小时后，90.1%已被利用，并观察到乙酸、琥珀酸、乳酸和丁酸的产生。LNT2 特异性增加了 、以及 的丰度。GOS/inulin 混合物中的 GOS 在 14 小时后完全发酵，而菊粉只有低 DP 在 14 小时后迅速被利用。为了确定发酵是否会导致共生菌对肠道上皮细胞的定植增强，我们研究了共生菌 对 Caco-2 细胞的粘附。收集 LNT2 发酵消化物在 14 小时、24 小时和 36 小时后，以及 GOS/inulin 在发酵 24 小时后，显著增加了 对 Caco-2 细胞的粘附，而 3-FL 则没有这种作用。我们的研究结果表明，hMO 的发酵非常依赖于结构，与常用的 GOS/菊粉不同，这可能导致对共生细胞与肠道上皮粘附的不同刺激能力，从而导致微生物定植的差异。这一知识可能有助于设计含有特定 hMO 分子的定制婴儿配方奶粉，以满足婴儿从母乳喂养到配方奶粉过渡期间的需求。
