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母乳 N-聚糖核心岩藻糖基化通过选择性促进肠道 spp. 和 spp. 的 l-岩藻糖代谢来激活 B 细胞

Core Fucosylation of Maternal Milk N-Glycan Evokes B Cell Activation by Selectively Promoting the l-Fucose Metabolism of Gut spp. and spp.

机构信息

College of Basic Medical Science, Dalian Medical University, Dalian, China

College of Basic Medical Science, Dalian Medical University, Dalian, China.

出版信息

mBio. 2019 Apr 2;10(2):e00128-19. doi: 10.1128/mBio.00128-19.

Abstract

The maternal milk glycobiome is crucial for shaping the gut microbiota of infants. Although high core fucosylation catalyzed by fucosyltransferase 8 (Fut8) is a general feature of human milk glycoproteins, its role in the formation of a healthy microbiota has not been evaluated. In this study, we found that the core-fucosylated N-glycans in milk of Chinese mothers selectively promoted the colonization of specific gut microbial groups, such as spp. and spp. in their breast-fed infants during lactation. Compared with (WT) mouse-fed neonates, the offspring fed by maternal mice had a distinct gut microbial profile, which was featured by a significant reduction of spp., spp., and spp. and increased abundance of members of the NK4A136 group and spp. Moreover, these offspring mice showed a lower proportion of splenic CD19 CD69 B lymphocytes and attenuated humoral immune responses upon ovalbumin (OVA) immunization. studies demonstrated that the chemically synthesized core-fucosylated oligosaccharides possessed the ability to promote the growth of tested and strains in minimal medium. The resulting L-fucose metabolites, lactate and 1,2-propanediol, could promote the activation of B cells via the B cell receptor (BCR)-mediated signaling pathway. This study provides novel evidence for the critical role of maternal milk protein glycosylation in shaping early-life gut microbiota and promoting B cell activation of neonates. The special core-fucosylated oligosaccharides might be promising prebiotics for the personalized nutrition of infants.

摘要

母乳糖组学对于塑造婴儿肠道微生物群至关重要。虽然高核心岩藻糖基化(由岩藻糖基转移酶 8(Fut8)催化)是人类乳蛋白聚糖的普遍特征,但它在形成健康微生物群中的作用尚未得到评估。在这项研究中,我们发现中国母亲母乳中的核心岩藻糖基化 N-聚糖选择性地促进了特定肠道微生物群的定植,例如哺乳期婴儿中的 spp. 和 spp.。与 (WT)小鼠喂养的新生儿相比,由 母鼠喂养的后代具有明显不同的肠道微生物群谱,其特征是 spp.、 spp. 和 spp. 的丰度显著降低,而 NK4A136 组和 spp. 的丰度增加。此外,这些后代小鼠脾脏中 CD19 CD69 B 淋巴细胞的比例较低,并且在卵清蛋白(OVA)免疫时体液免疫反应减弱。 研究表明,化学合成的核心岩藻糖基化寡糖具有在最小培养基中促进测试的 和 菌株生长的能力。所得的 L-岩藻糖代谢产物乳酸和 1,2-丙二醇可通过 B 细胞受体(BCR)介导的信号通路促进 B 细胞的激活。这项研究为母乳蛋白糖基化在塑造早期生命肠道微生物群和促进新生儿 B 细胞激活方面的关键作用提供了新的证据。特殊的核心岩藻糖基化寡糖可能是婴儿个性化营养的有前途的益生元。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9f5/6445936/4d77a2888b8a/mBio.00128-19-f0001.jpg

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