Early infancy microbial and metabolic alterations affect risk of childhood asthma
Early infancy microbial and metabolic alterations affect risk of childhood asthma
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DOI：
10.1126/scitranslmed.aab2271
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发表时间：
2015-09-30
影响因子：
17.1
通讯作者：
Finlay, B. Brett
中科院分区：
文献类型：
--
作者：
Arrieta, Marie-Claire;Stiemsma, Leah T.;Finlay, B. Brett
哮喘是最常见的儿科慢性疾病，影响全球3亿多人。最近在小鼠中的证据已经确定了生命早期的“关键窗口”，其中肠道微生物变化（生态失调）对实验性哮喘最有影响。然而，目前的研究尚未确定这些变化是否先于或参与人类哮喘。我们比较了参加加拿大健康婴儿纵向发育（CHILD）研究的319名受试者的肠道微生物群，结果表明，有哮喘风险的婴儿在出生后的前100天内表现出短暂的肠道微生物生态失调。在有哮喘风险的儿童中，毛螺菌属、韦荣氏球菌属、粪杆菌属和罗氏菌属的相对丰度显著降低。这种细菌类群的减少伴随着粪便乙酸盐水平的降低和肝肠代谢产物的失调。用这四种细菌类群接种无菌小鼠可改善其成年后代的气道炎症，证明这些细菌类群在避免哮喘发展中的因果作用。这些结果增强了未来基于微生物的诊断和治疗的潜力，可能以益生菌的形式，以预防儿童哮喘和其他相关过敏性疾病的发展。
Asthma is the most prevalent pediatric chronic disease and affects more than 300 million people worldwide. Recent evidence in mice has identified a "critical window" early in life where gut microbial changes (dysbiosis) are most influential in experimental asthma. However, current research has yet to establish whether these changes precede or are involved in human asthma. We compared the gut microbiota of 319 subjects enrolled in the Canadian Healthy Infant Longitudinal Development (CHILD) Study, and show that infants at risk of asthma exhibited transient gut microbial dysbiosis during the first 100 days of life. The relative abundance of the bacterial genera Lachnospira, Veillonella, Faecalibacterium, and Rothia was significantly decreased in children at risk of asthma. This reduction in bacterial taxa was accompanied by reduced levels of fecal acetate and dysregulation of enterohepatic metabolites. Inoculation of germ-free mice with these four bacterial taxa ameliorated airway inflammation in their adult progeny, demonstrating a causal role of these bacterial taxa in averting asthma development. These results enhance the potential for future microbe-based diagnostics and therapies, potentially in the form of probiotics, to prevent the development of asthma and other related allergic diseases in children.