Dysbiotic lung microbial communities of neonates from allergic mothers confer neonate responsiveness to suboptimal allergen.

Dysbiotic lung microbial communities of neonates from allergic mothers confer neonate responsiveness to suboptimal allergen.
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DOI:
10.3389/falgy.2023.1135412
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发表时间:
2023
影响因子:
--
通讯作者:
Cook-Mills, Joan M.
Cook-Mills, Joan M.
中科院分区:
其他
文献类型:
--
作者:
Bloodworth, Jeffery C.;Hoji, Aki;Wolff, Garen;Mandal, Rabindra K.;Schmidt, Nathan W.;Deshane, Jessy S.;Morrow, Casey D.;Kloepfer, Kirsten M.;Cook-Mills, Joan M.

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在人类和动物中,过敏母亲的后代对过敏原的反应增加。在小鼠中,母体补充α-生育酚(αT)可阻断这一作用。此外,患有过敏性哮喘的成人和儿童气道微生物群失调,变形菌群增加,拟杆菌群减少。目前尚不清楚αT是否会改变新生儿肺部微生物群失调的发展,或者新生儿肺部失调是否会改变过敏的发展。为了解决这个问题,研究人员对基础饲粮或α t补充饲粮中过敏和非过敏母鼠的幼崽进行了16S rRNA基因分析(细菌微生物组)。在过敏原刺激前后,过敏母鼠的肺微生物组成失调,变形菌群增加,拟杆菌群减少,αT的补充可以抑制这种情况。我们确定了气管内转移幼犬肺部益生菌群落是否会改变幼犬早期过敏的发展。有趣的是,从过敏母亲的新生儿转移到非过敏母亲的新生儿的肺部微生物群落足以使受体幼崽对过敏原产生反应。相比之下,无论是非过敏母亲的新生儿还是补充α t的过敏母亲的新生儿,供体肺微生物群落的转移都不能保护过敏母亲的新生儿免受过敏的影响。这些数据表明,益生不良的肺部微生物群占主导地位,足以增强新生儿对过敏原的反应。重要的是,在enhance队列中,具有抗炎特征的生育酚同工型的婴儿与具有促炎特征的生育酚同工型的婴儿相比,其微生物组组成发生了改变。这些数据可以为未来研究的设计提供信息,以预防或干预生命早期哮喘和过敏性疾病的方法。
In humans and animals, offspring of allergic mothers have increased responsiveness to allergens. This is blocked in mice by maternal supplementation with α-tocopherol (αT). Also, adults and children with allergic asthma have airway microbiome dysbiosis with increased Proteobacteria and may have decreased Bacteroidota. It is not known whether αT alters neonate development of lung microbiome dysbiosis or whether neonate lung dysbiosis modifies development of allergy. To address this, the bronchoalveolar lavage was analyzed by 16S rRNA gene analysis (bacterial microbiome) from pups of allergic and non-allergic mothers with a basal diet or αT-supplemented diet. Before and after allergen challenge, pups of allergic mothers had dysbiosis in lung microbial composition with increased Proteobacteria and decreased Bacteroidota and this was blocked by αT supplementation. We determined whether intratracheal transfer of pup lung dysbiotic microbial communities modifies the development of allergy in recipient pups early in life. Interestingly, transfer of dysbiotic lung microbial communities from neonates of allergic mothers to neonates of non-allergic mothers was sufficient to confer responsiveness to allergen in the recipient pups. In contrast, neonates of allergic mothers were not protected from development of allergy by transfer of donor lung microbial communities from either neonates of non-allergic mothers or neonates of αT-supplemented allergic mothers. These data suggest that the dysbiotic lung microbiota is dominant and sufficient for enhanced neonate responsiveness to allergen. Importantly, infants within the INHANCE cohort with an anti-inflammatory profile of tocopherol isoforms had an altered microbiome composition compared to infants with a pro-inflammatory profile of tocopherol isoforms. These data may inform design of future studies for approaches in the prevention or intervention in asthma and allergic disease early in life.
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