Michael Smith Laboratories and the Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada; Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada; Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada.
Facultad de Ciencias Medicas, de la Salud y la Vida, Universidad Internacional del Ecuador, Quito, Ecuador.
J Allergy Clin Immunol. 2018 Aug;142(2):424-434.e10. doi: 10.1016/j.jaci.2017.08.041. Epub 2017 Dec 11.
Asthma is the most prevalent chronic disease of childhood. Recently, we identified a critical window early in the life of both mice and Canadian infants during which gut microbial changes (dysbiosis) affect asthma development. Given geographic differences in human gut microbiota worldwide, we studied the effects of gut microbial dysbiosis on atopic wheeze in a population living in a distinct developing world environment.
We sought to determine whether microbial alterations in early infancy are associated with the development of atopic wheeze in a nonindustrialized setting.
We conducted a case-control study nested within a birth cohort from rural Ecuador in which we identified 27 children with atopic wheeze and 70 healthy control subjects at 5 years of age. We analyzed bacterial and eukaryotic gut microbiota in stool samples collected at 3 months of age using 16S and 18S sequencing. Bacterial metagenomes were predicted from 16S rRNA data by using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States and categorized by function with Kyoto Encyclopedia of Genes and Genomes ontology. Concentrations of fecal short-chain fatty acids were determined by using gas chromatography.
As previously observed in Canadian infants, microbial dysbiosis at 3 months of age was associated with later development of atopic wheeze. However, the dysbiosis in Ecuadorian babies involved different bacterial taxa, was more pronounced, and also involved several fungal taxa. Predicted metagenomic analysis emphasized significant dysbiosis-associated differences in genes involved in carbohydrate and taurine metabolism. Levels of the fecal short-chain fatty acids acetate and caproate were reduced and increased, respectively, in the 3-month stool samples of children who went on to have atopic wheeze.
Our findings support the importance of fungal and bacterial microbiota during the first 100 days of life on the development of atopic wheeze and provide additional support for considering modulation of the gut microbiome as a primary asthma prevention strategy.
哮喘是儿童中最常见的慢性疾病。最近，我们发现，在老鼠和加拿大婴儿的生命早期都存在一个关键窗口期，在此期间，肠道微生物的变化（失调）会影响哮喘的发展。鉴于全球人类肠道微生物群存在地域差异，我们在一个生活在独特发展中世界环境的人群中研究了肠道微生物失调对特应性喘息的影响。
我们旨在确定在非工业化环境中，婴儿早期的微生物改变是否与特应性喘息的发展有关。
我们在厄瓜多尔农村进行了一项病例对照研究，该研究是在一个出生队列中进行的，在该队列中，我们在 5 岁时确定了 27 名特应性喘息儿童和 70 名健康对照者。我们使用 16S 和 18S 测序分析了 3 个月龄时采集的粪便样本中的细菌和真核肠道微生物群。通过使用 Phylogenetic Investigation of Communities by Reconstruction of Unobserved States 从 16S rRNA 数据预测细菌宏基因组，并通过京都基因与基因组百科全书本体论对其功能进行分类。通过气相色谱法测定粪便短链脂肪酸的浓度。
与加拿大婴儿之前的观察结果一样，3 个月时的微生物失调与以后特应性喘息的发展有关。然而，厄瓜多尔婴儿的失调涉及不同的细菌类群，更为明显，并且还涉及几个真菌类群。预测的宏基因组分析强调了参与碳水化合物和牛磺酸代谢的基因存在显著的失调相关差异。在以后发生特应性喘息的儿童的 3 个月粪便样本中，粪便短链脂肪酸乙酸盐和己酸盐的水平分别降低和增加。
我们的研究结果支持生命前 100 天内真菌和细菌微生物群对特应性喘息发展的重要性，并进一步支持将调节肠道微生物群作为预防哮喘的主要策略。
