The gut microbiome elicits antigen-specific immunoglobulin G (IgG) at steady state that cross-reacts to pathogens to confer protection against systemic infection. The role of gut microbiome–specific IgG antibodies in the development of the gut microbiome and immunity against enteric pathogens in early life, however, remains largely undefined. In this study, we show that gut microbiome–induced maternal IgG is transferred to the neonatal intestine through maternal milk via the neonatal Fc receptor and directly inhibits Citrobacter rodentium colonization and attachment to the mucosa. Enhanced neonatal immunity against oral C. rodentium infection was observed after maternal immunization with a gut microbiome–derived IgG antigen, outer membrane protein A, or induction of IgG-inducing gut bacteria. Furthermore, by generating a gene-targeted mouse model with complete IgG deficiency, we demonstrate that IgG knockout neonates are more susceptible to C. rodentium infection and exhibit alterations of the gut microbiome that promote differentiation of interleukin-17A–producing γδ T cells in the intestine, which persist into adulthood and contribute to increased disease severity in a dextran sulfate sodium–induced mouse model of colitis. Together, our studies have defined a critical role for maternal gut microbiome–specific IgG antibodies in promoting immunity against enteric pathogens and shaping the development of the gut microbiome and immune cells in early life.

中文翻译：

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母体肠道微生物组诱导的 IgG 调节新生儿肠道微生物组和免疫

肠道微生物组在稳定状态下引发抗原特异性免疫球蛋白 G (IgG)，与病原体发生交叉反应，从而提供针对全身感染的保护。然而，肠道微生物组特异性 IgG 抗体在早期肠道微生物组的发育和对肠道病原体的免疫中的作用在很大程度上仍未确定。在这项研究中，我们表明肠道微生物组诱导的母体 IgG 通过新生儿 Fc 受体通过母乳转移到新生儿肠道，并直接抑制柠檬酸杆菌定植和附着于黏膜。增强新生儿对口腔的免疫力C. 啮齿目在使用肠道微生物组衍生的 IgG 抗原、外膜蛋白 A 或诱导 IgG 诱导肠道细菌进行母体免疫后观察到感染。此外，通过生成具有完全 IgG 缺陷的基因靶向小鼠模型，我们证明 IgG 敲除新生儿更容易受到C. 啮齿目感染并表现出肠道微生物组的改变，促进肠道中产生白细胞介素 17A 的 γδ T 细胞的分化，这些细胞持续到成年期并导致葡聚糖硫酸钠诱导的结肠炎小鼠模型中疾病严重程度增加。总之，我们的研究确定了母体肠道微生物组特异性 IgG 抗体在促进对肠道病原体的免疫力和塑造早期肠道微生物组和免疫细胞发育方面的关键作用。