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Development of the gut microbiota and mucosal IgA responses in twins and gnotobiotic mice

机译：双胞胎和gnotobiotic小鼠肠道微生物群和粘膜IgA反应的发展。

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摘要

Immunoglobulin A (IgA), the major class of antibody secreted by the gut mucosa, is an important contributor to gut barrier function(1-3). The repertoire of IgA bound to gut bacteria reflects both T-cell-dependent and -independent pathways(4,5), plus glycans present on the antibody's secretory component(6). Human gut bacterial taxa targeted by IgA in the setting of barrier dysfunction are capable of producing intestinal pathology when isolated and transferred to gnotobiotic mice(7,8). A complex reorientation of gut immunity occurs as infants transition from passively acquired IgA present in breast milk to host-derived IgA(9-11). How IgA responses co-develop with assembly of the microbiota during this period remains poorly understood. Here, we (1) identify a set of age-discriminatory bacterial taxa whose representations define a program of microbiota assembly and maturation during the first 2 postnatal years that is shared across 40 healthy twin pairs in the USA; (2) 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 (3) 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 faecal 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. Most 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 to help discover ways of repairing or preventing perturbations in this facet of host immunity.
机译：免疫球蛋白A（IgA）是肠道粘膜分泌的主要抗体类别，是肠道屏障功能的重要贡献者（1-3）。与肠道细菌结合的IgA的库反映了T细胞依赖性和非依赖性途径（4,5），以及抗体分泌成分上存在的聚糖（6）。 IgA靶向的人肠道细菌分类群在屏障功能障碍的情况下能够被分离并转移到致生性小鼠中而产生肠道病理（7,8）。随着婴儿从母乳中被动获得的IgA过渡到宿主来源的IgA，肠道免疫发生了复杂的重新定向（9-11）。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（1）识别出一组具有年龄区分性的细菌类群，这些类群的定义定义了出生后前2年内微生物群落的组装和成熟程序，该程序在美国的40对健康双胞胎中共享。 （2）描述了肠道粘膜IgA对微生物群细菌成员反应的进展模式，这种模式在出生后的头几个月对家庭成员（双胞胎）非常有特色，然后在第二年在各对之间普遍存在。 （3）评估合子性，分娩方式和母乳喂养的影响。这些IgA反应的与年龄相关的差异可以在年轻的无菌小鼠中概括，用从两个双胞胎对分别在6和18个月大时获得的粪便微生物群定居，并喂养一系列人类饮食，模拟从牛奶喂养到辅食。这些反应中的大多数对饮食具有鲁棒性，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粘膜免疫发展，并有助于发现修复或预防宿主免疫这一方面摄动的方法。

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  • 来源
    《Nature》 |2016年第7606期|263-266|共4页
  • 作者

    Planer Joseph D.; Peng Yangqing; Kau Andrew L.; Blanton Laura V.; Ndao I. Malick; Tarr Phillip I.; Warner Barbara B.; Gordon Jeffrey I.;

  • 作者单位

    Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63110 USA|Washington Univ, Ctr Gut Microbiome & Nutr Res, Sch Med, St Louis, MO 63110 USA;

    Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63110 USA|Washington Univ, Ctr Gut Microbiome & Nutr Res, Sch Med, St Louis, MO 63110 USA;

    Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63110 USA|Washington Univ, Ctr Gut Microbiome & Nutr Res, Sch Med, St Louis, MO 63110 USA;

    Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63110 USA|Washington Univ, Ctr Gut Microbiome & Nutr Res, Sch Med, St Louis, MO 63110 USA;

    Washington Univ, Dept Pediat, Sch Med, St Louis, MO 63110 USA;

    Washington Univ, Dept Pediat, Sch Med, St Louis, MO 63110 USA;

    Washington Univ, Dept Pediat, Sch Med, St Louis, MO 63110 USA;

    Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63110 USA|Washington Univ, Ctr Gut Microbiome & Nutr Res, Sch Med, St Louis, MO 63110 USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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