Division of Infectious Disease, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Division of Infectious Disease, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Perlman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Cell Host Microbe. 2023 Apr 12;31(4):554-570.e7. doi: 10.1016/j.chom.2023.03.006. Epub 2023 Mar 29.
Disruptions to the intestinal microbiome during weaning lead to negative effects on host immune function. However, the critical host-microbe interactions during weaning that are required for immune system development remain poorly understood. We find that restricting microbiome maturation during weaning stunts immune system development and increases susceptibility to enteric infection. We developed a gnotobiotic mouse model of the early-life microbiome Pediatric Community (PedsCom). These mice develop fewer peripheral regulatory T cells and less IgA, hallmarks of microbiota-driven immune system development. Furthermore, adult PedsCom mice retain high susceptibility to Salmonella infection, which is characteristic of young mice and children. Altogether, our work illustrates how the post-weaning transition in microbiome composition contributes to normal immune maturation and protection from infection. Accurate modeling of the pre-weaning microbiome provides a window into the microbial requirements for healthy development and suggests an opportunity to design microbial interventions at weaning to improve immune development in human infants.
断奶期间肠道微生物组的紊乱会对宿主免疫功能产生负面影响。然而，对于免疫发育所需的关键宿主-微生物相互作用仍知之甚少。我们发现，在断奶期间限制微生物组的成熟会阻碍免疫系统的发育，并增加对肠道感染的易感性。我们开发了一种小儿社区（PedsCom）早期生活微生物组的无菌小鼠模型。这些小鼠外周调节性 T 细胞和 IgA 较少，这是微生物驱动的免疫系统发育的标志。此外，成年 PedsCom 小鼠仍然容易感染沙门氏菌，这是幼鼠和儿童的特征。总之，我们的工作说明了微生物组组成在断奶后的转变如何促进正常的免疫成熟和免受感染。对出生前微生物组的准确建模为健康发育的微生物需求提供了一个窗口，并为在断奶时设计微生物干预措施以改善人类婴儿的免疫发育提供了机会。
