Development of the gut microbiota and mucosal IgA responses in twins and gnotobiotic mice.
Development of the gut microbiota and mucosal IgA responses in twins and gnotobiotic mice.
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DOI：
10.1038/nature17940
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发表时间：
2016-06-09
期刊：
影响因子：
64.8
通讯作者：
Gordon JI
中科院分区：
文献类型：
--
作者：
Planer JD;Peng Y;Kau AL;Blanton LV;Ndao IM;Tarr PI;Warner BB;Gordon JI
免疫球蛋白A （IgA）是肠道黏膜分泌的一类主要抗体，对肠道屏障功能起着重要作用。与肠道细菌结合的IgA库反映了T细胞依赖性和非依赖性途径，以及存在于抗体分泌成分上的聚糖。在肠道屏障功能障碍的情况下，IgA靶向的人肠道细菌分类群在分离并转移到非生物小鼠时能够产生肠道病理。当婴儿从母乳中被动获得的IgA过渡到宿主来源的IgA时，肠道免疫发生了复杂的重新定位。在此期间，IgA反应如何与微生物群的组装共同发展仍然知之甚少。在这里，我们(i)确定了一组年龄歧视的细菌分类群，其代表定义了40对健康的美国双胞胎在出生后的头2年里共享的微生物群组装/成熟程序；（ii）描述肠道黏膜IgA对微生物群细菌成员反应的进展模式，该模式在出生后的前几个月对家庭成员（双胞胎）具有高度独特性，然后在第二年在成对中推广；(3)评估合子性、生育方式和母乳喂养的影响。这些IgA反应的年龄相关差异可以在年轻的无菌小鼠中重现，这些小鼠用从6个月和18个月大的两对双胞胎中获得的粪便微生物群定植，并喂养一系列模拟从牛奶喂养到辅食过渡的人类饮食。这些反应中的大多数对饮食是稳健的，这表明社区成员的“内在”特性在决定IgA反应中起主导作用。所描述的方法可用于定义健康和疾病状态下的肠道黏膜免疫发育，并有助于发现修复或预防宿主免疫这方面扰动的方法。
Immunoglobulin A (IgA), the major class of antibody secreted by the gut mucosa, is an important contributor to gut barrier function. The repertoire of IgA bound to gut bacteria reflects both T cell-dependent and -independent pathways, plus glycans present on the antibody’s secretory component. Human gut bacterial taxa targeted by IgA in the setting of intestinal barrier dysfunction are capable of producing intestinal pathology when isolated and transferred to gnotobiotic mice. A complex reorientation of gut immunity occurs as infants transition from passively acquired IgA present in breast milk to host-derived IgA. How IgA responses co-develop with assembly of the microbiota during this period remains poorly understood. Here, we (i) identify a set of age-discriminatory bacterial taxa whose representations define a program of microbiota assembly/maturation during the first 2 postnatal years that is shared across 40 healthy USA twin pairs; (ii) describe a pattern of progression of gut mucosal IgA responses to bacterial members of the microbiota that is highly distinctive for family members (twin pairs) during the first several postnatal months then generalizes across pairs in the second year; and (iii) assess the effects of zygosity, birth mode and breast feeding. Age-associated differences in these IgA responses can be recapitulated in young germ-free mice, colonized with fecal microbiota obtained from two twin pairs at 6 and 18 months of age, and fed a sequence of human diets that simulate the transition from milk feeding to complementary foods. The majority of these responses were robust to diet suggesting that ‘intrinsic’ properties of community members play a dominant role in dictating IgA responses. The approach described can be used to define gut mucosal immune development in health and disease states and help discover ways for repairing or preventing perturbations in this facet of host immunity.