人乳中分泌型和非分泌型母亲的微生物群会影响小鼠的肠道和免疫系统。

UNLABELLED: Maternal secretor status is one of the determinants of human milk oligosaccharides (HMOs) composition, which, in turn, influences the gut microbiota composition of infants. To understand if this change in gut microbiota impacts immune cell composition, intestinal morphology, and gene expression, 21-day-old germ-free C57BL/6 mice were transplanted with fecal microbiota from infants whose mothers were either secretors (SMM) or non-secretors (NSM) or from infants consuming dairy-based formula (MFM). For each group, one set of mice was supplemented with HMOs. HMO supplementation did not significantly impact the microbiota diversity; however, SMM mice had a higher abundance of genus , , and , whereas, in the NSM group, there was a higher abundance of , , and . In MFM, gut microbiota was represented mainly by , , and . In mesenteric lymph node, Foxp3+ T cells and innate lymphoid cells type 2 were increased in MFM mice supplemented with HMOs, while in the spleen, they were increased in SMM + HMOs mice. Similarly, serum immunoglobulin A was also elevated in MFM + HMOs group. Distinct global gene expression of the gut was observed in each microbiota group, which was enhanced with HMOs supplementation. Overall, our data show that distinct infant gut microbiota due to maternal secretor status or consumption of dairy-based formula and HMO supplementation impacts immune cell composition, antibody response, and intestinal gene expression in a mouse model. IMPORTANCE: Early life factors like neonatal diet modulate gut microbiota, which is important for the optimal gut and immune function. One such factor, human milk oligosaccharides (HMOs), the composition of which is determined by maternal secretor status, has a profound effect on infant gut microbiota. However, how the infant gut microbiota composition determined by maternal secretor status or consumption of infant formula devoid of HMOs impacts infant intestinal ammorphology, gene expression, and immune signature is not well explored. This study provides insights into the differential establishment of infant microbiota derived from infants fed by secretor or non-secretor mothers milk or those consuming infant formula and demonstrates that the secretor status of mothers promotes Bifidobacteria and Bacteroides sps. establishment. This study also shows that supplementation of pooled HMOs in mice changed immune cell composition in the spleen and mesenteric lymph nodes and immunoglobulins in circulation. Hence, this study highlights that maternal secretor status has a role in infant gut microbiota composition, and this, in turn, can impact host gut and immune system.

未加说明：母体分泌状态是人类乳寡糖（HMOs）组成的决定因素之一，而 HMOs 组成又会影响婴儿肠道微生物群的组成。为了了解肠道微生物群的这种变化是否会影响免疫细胞组成、肠道形态和基因表达，将 21 日龄无菌 C57BL/6 小鼠移植了来自母亲为分泌型（SMM）或非分泌型（NSM）的婴儿或食用基于乳制品配方（MFM）的婴儿的粪便微生物群。对于每个组，一组小鼠补充了 HMOs。HMO 补充并没有显著影响微生物多样性；然而，SMM 小鼠中属、和的丰度更高，而在 NSM 组中，属、和的丰度更高。在 MFM 中，肠道微生物群主要由、和代表。在肠系膜淋巴结中，补充 HMOs 的 MFM 小鼠中 Foxp3+T 细胞和 2 型固有淋巴细胞增加，而在 SMM + HMOs 小鼠中，在脾脏中增加。同样，血清免疫球蛋白 A 在 MFM + HMOs 组中也升高。在每个微生物群组中都观察到肠道的独特全基因表达，而补充 HMOs 后则增强了这种表达。总的来说，我们的数据表明，由于母体分泌状态或食用基于乳制品的配方和 HMO 补充而导致的不同婴儿肠道微生物群会影响免疫细胞组成、抗体反应和肠道基因表达在小鼠模型中。

重要性：新生儿饮食等早期生活因素会调节肠道微生物群，这对肠道和免疫功能的最佳状态很重要。HMOs 就是这样一种因素，它的组成由母体分泌状态决定，对婴儿肠道微生物群有深远的影响。然而，由母体分泌状态或食用不含 HMOs 的婴儿配方奶粉决定的婴儿肠道微生物群组成如何影响婴儿肠道形态、基因表达和免疫特征尚不清楚。本研究深入探讨了源自分泌型或非分泌型母亲母乳喂养或食用婴儿配方奶粉的婴儿的不同婴儿肠道微生物群的建立，并表明母亲的分泌状态促进双歧杆菌和拟杆菌属的建立。本研究还表明，在小鼠中补充混合 HMOs 会改变脾脏和肠系膜淋巴结中的免疫细胞组成以及循环中的免疫球蛋白。因此，本研究强调了母体分泌状态在婴儿肠道微生物群组成中的作用，而这反过来又会影响宿主的肠道和免疫系统。