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首页> 外文期刊>Nature >Neonatal selection by Toll-like receptor 5 influences long-term gut microbiota composition
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Neonatal selection by Toll-like receptor 5 influences long-term gut microbiota composition

机译：Toll样受体5对新生儿的选择会影响长期肠道菌群的组成

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摘要

Alterations in enteric microbiota are associated with several highly prevalent immune-mediated and metabolic diseases(1-3), and experiments involving faecal transplants have indicated that such alterations have a causal role in at least some such conditions(4-6). The postnatal period is particularly critical for the development of microbiota composition, host-microbe interactions and immune homeostasis(7-9). However, the underlying molecular mechanisms of this neonatal priming period have not been defined. Here we report the identification of a host-mediated regulatory circuit of bacterial colonization that acts solely during the early neonatal period but influences life-long microbiota composition. We demonstrate age-dependent expression of the flagellin receptor Toll-like receptor 5 (TLR5) in the gut epithelium of neonate mice. Using competitive colonization experiments, we demonstrate that epithelial TLR5-mediated REG3 gamma production is critical for the counter-selection of colonizing flagellated bacteria. Comparative microbiota transfer experiments in neonate and adult wild-type and Tlr5-deficient germ-free mice reveal that neonatal TLR5 expression strongly influences the composition of the microbiota throughout life. Thus, the beneficial microbiota in the adult host is shaped during early infancy. This might explain why environmental factors that disturb the establishment of the microbiota during early life can affect immune homeostasis and health in adulthood.
机译：肠道菌群的改变与几种高度流行的免疫介导的和代谢性疾病有关（1-3），而涉及粪便移植的实验表明，这种改变在至少某些此类疾病中具有因果作用（4-6）。产后时期对于微生物群组成，宿主-微生物相互作用和免疫稳态的发展尤为关键（7-9）。但是，尚未确定该新生儿启动期的潜在分子机制。在这里，我们报告鉴定的细菌定植的宿主介导的调节电路仅在新生儿早期起作用，但会影响终身的微生物群组成。我们证明新生小鼠的肠道上皮中鞭毛蛋白受体Toll样受体5（TLR5）的年龄依赖性表达。使用竞争性定植实验，我们证明了上皮TLR5介导的REG3γ产生对于定殖定殖鞭毛细菌的反选择至关重要。在新生和成年野生型以及Tlr5缺陷型无菌小鼠中进行的比较菌群转移实验表明，新生儿TLR5的表达在整个生命中都强烈影响菌群的组成。因此，成年宿主中的有益菌群在婴儿早期就成型。这也许可以解释为什么在生命早期干扰微生物群建立的环境因素会影响免疫稳态和成年期健康。

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  • 来源
    《Nature》 |2018年第7719期|489-493|共5页
  • 作者

    Fulde Marcus; Sommer Felix; Chassaing Benoit; van Vorst Kira; Dupont Aline; Hensel Michael; Basic Marijana; Klopfleisch Robert; Rosenstiel Philip; Bleich Andre; Baeckhed Fredrik; Gewirtz Andrew T.; Hornef Mathias W.;

  • 作者单位

    Hannover Med Sch, Inst Med Microbiol & Hosp Epidemiol, Hannover, Germany;

    Univ Gothenburg, Dept Mol & Clin Med, Wallenberg Lab, Inst Med, Gothenburg, Sweden;

    Georgia State Univ, Inst Neurosci, Atlanta, GA 30303 USA;

    Free Univ Berlin, Dept Vet Med, Inst Microbiol & Epizoot, Berlin, Germany;

    RWTH Univ Hosp Aachen, Inst Med Microbiol, Aachen, Germany;

    Univ Osnabruck, Div Microbiol, Osnabruck, Germany;

    Hannover Med Sch, Inst Lab Anim Sci, Hannover, Germany;

    Free Univ Berlin, Dept Vet Med, Inst Vet Pathol, Berlin, Germany;

    Univ Kiel, Inst Clin Mol Biol IKMB, Kiel, Germany;

    Hannover Med Sch, Inst Lab Anim Sci, Hannover, Germany;

    Univ Gothenburg, Dept Mol & Clin Med, Wallenberg Lab, Inst Med, Gothenburg, Sweden;

    Georgia State Univ, Inst Biomed Sci, Atlanta, GA 30303 USA;

    Hannover Med Sch, Inst Med Microbiol & Hosp Epidemiol, Hannover, Germany;

  • 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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