Antibiotics (Abx) are administered to 20%–30% of pregnant women, but their effects on neonatal immune development are poorly understood. We show that newborn mice born to Abx-treated dams are more susceptible to late-onset sepsis. This susceptibility is linked to lower maternal breast milk immunoglobulin A (IgA), neonatal fecal IgA, and IgA coating of intestinal bacteria, thus causing the translocation of intestinal pathobionts. Weaned young adults born to Abx-treated mothers had reduced IgA+ plasma cells in the ileum and colon, fecal secretory IgA (SIgA), colonic CD4+ T regulatory lymphocytes and T helper 17-like lymphocytes, and a less diverse fecal microbiome. However, treatment with apyrase, which restores SIgA secretion, prompted IgA production in breast milk and protected pups from sepsis. Additionally, breast milk from untreated mothers rescued the phenotypes of pups born to Abx-treated mothers. Our data highlight the impact of prenatal Abx on breast milk IgA and their long-term influence on intestinal mucosal immune function mediated by breastfeeding.

中文翻译：

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产前抗生素可降低母乳 IgA 并诱导小鼠后代菌群失调，从而增加新生儿对细菌性败血症的易感性


20%-30% 的孕妇使用抗生素 （Abx），但对其对新生儿免疫发育的影响知之甚少。我们表明，Abx 处理的母体所生的新生小鼠更容易患晚发性败血症。这种易感性与母乳免疫球蛋白 A （IgA） 、新生儿粪便 IgA 和肠道细菌 IgA 涂层较低有关，从而导致肠道致病因子易位。Abx 治疗的母亲所生的断奶年轻成人回肠和结肠中的 IgA + 浆细胞、粪便分泌型 IgA （SIgA） 、结肠 CD4+ T 调节淋巴细胞和 T 辅助性 17 样淋巴细胞减少，粪便微生物组多样性较低。然而，用恢复 SIgA 分泌的双磷酸腺苷酶治疗促进了母乳中 IgA 的产生，并保护了幼崽免受败血症的侵害。此外，未经处理的母亲的母乳挽救了 Abx 处理的母亲所生幼崽的表型。我们的数据强调了产前 Abx 对母乳 IgA 的影响及其对母乳喂养介导的肠道粘膜免疫功能的长期影响。