Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada. Department of Microbiology & Immunology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
Department of Microbiology & Immunology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada. Child & Family Research Institute and BC Children's Hospital, Vancouver, British Columbia V4Z 4H4, Canada.
Sci Transl Med. 2015 Sep 30;7(307):307ra152. doi: 10.1126/scitranslmed.aab2271.
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.
哮喘是最常见的儿科慢性疾病，影响着全球超过 3 亿人。最近在小鼠身上的证据表明，生命早期存在一个“关键窗口期”，在此期间，肠道微生物的变化（失调）对实验性哮喘的影响最大。然而，目前的研究尚未确定这些变化是先于还是参与了人类哮喘的发生。我们比较了加拿大健康婴儿纵向发展（CHILD）研究中 319 名受试者的肠道微生物群，并表明哮喘风险婴儿在生命的头 100 天内表现出短暂的肠道微生物失调。在哮喘风险儿童中，细菌属lachnospira、veillonella、faecalibacterium 和 rothia 的相对丰度显著降低。细菌分类群的减少伴随着粪便乙酸水平降低和肠肝代谢物失调。将这四种细菌分类群接种到无菌小鼠中，可改善其成年后代的气道炎症，表明这些细菌分类群在避免哮喘发展方面具有因果关系。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，预防儿童哮喘和其他相关过敏性疾病的发展。
