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Fecal IgA Levels Are Determined by Strain-Level Differences in Bacteroides ovatus and Are Modifiable by Gut Microbiota Manipulation.
Cell Host & Microbe ( IF 20.6 ) Pub Date : 2020-02-18 , DOI: 10.1016/j.chom.2020.01.016
Chao Yang 1 , Ilaria Mogno 1 , Eduardo J Contijoch 1 , Joshua N Borgerding 2 , Varun Aggarwala 1 , Zhihua Li 3 , Sophia Siu 3 , Emilie K Grasset 4 , Drew S Helmus 5 , Marla C Dubinsky 5 , Saurabh Mehandru 2 , Andrea Cerutti 6 , Jeremiah J Faith 1
Affiliation  

Fecal IgA production depends on colonization by a gut microbiota. However, the bacterial strains that drive gut IgA production remain largely unknown. Here, we assessed the IgA-inducing capacity of a diverse set of human gut microbial strains by monocolonizing mice with each strain. We identified Bacteroides ovatus as the species that best induced gut IgA production. However, this induction varied bimodally across different B. ovatus strains. The high IgA-inducing B. ovatus strains preferentially elicited more IgA production in the large intestine through the T cell-dependent B cell-activation pathway. Remarkably, a low-IgA phenotype in mice could be robustly and consistently converted into a high-IgA phenotype by transplanting a multiplex cocktail of high IgA-inducing B. ovatus strains but not individual ones. Our results highlight the critical importance of microbial strains in driving phenotype variation in the mucosal immune system and provide a strategy to robustly modify a gut immune phenotype, including IgA production.

中文翻译:


粪便 IgA 水平由卵形拟杆菌菌株水平差异决定,并且可通过肠道微生物群操作进行修改。



粪便 IgA 的产生取决于肠道微生物群的定植。然而,驱动肠道 IgA 产生的细菌菌株仍然很大程度上未知。在这里,我们通过用每种菌株对小鼠进行单一定殖来评估多种人类肠道微生物菌株的 IgA 诱导能力。我们确定卵形拟杆菌是最能诱导肠道 IgA 产生的物种。然而,这种诱导在不同的卵形双歧杆菌菌株中存在双峰变化。高 IgA 诱导性的卵形 B. ovatus 菌株优先通过 T 细胞依赖性 B 细胞激活途径在大肠中引发更多 IgA 产生。值得注意的是,通过移植高 IgA 诱导的卵形双歧杆菌菌株(而非单个菌株)的多重混合物,可以将小鼠的低 IgA 表型稳健且一致地转化为高 IgA 表型。我们的结果强调了微生物菌株在驱动粘膜免疫系统表型变异方面的至关重要性,并提供了一种强有力地改变肠道免疫表型(包括 IgA 产生)的策略。
更新日期:2020-02-20
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