Stickley Sara A, Fang Zhi Yi, Ambalavanan Amirthagowri, Zhang Yang, Zacharias Amanda M, Petersen Charisse, Dai Darlene, Azad Meghan B, Brook Jeffrey R, Mandhane Piushkumar J, Simons Elinor, Moraes Theo J, Surette Michael G, Turvey Stuart E, Subbarao Padmaja, Duan Qingling
Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
School of Computing, Queen's University, Kingston, Ontario, Canada.
J Allergy Clin Immunol. 2025 Aug;156(2):433-448. doi: 10.1016/j.jaci.2025.03.018. Epub 2025 Apr 3.
Gut microbiota has been associated with health and susceptibility to childhood diseases, including asthma and allergies. However, the genomic factors contributing to interindividual variations in gut microbiota remain poorly understood.
We sought to integrate host genomics with early-life exposures to investigate main and interaction effects on gut microbiota during the first year of life. In addition, we identified gut microbes associated with childhood respiratory (asthma, wheeze) and atopic (atopic dermatitis, food/inhalant sensitization) outcomes.
We leveraged microbiome data from infant stool at ages 3 months (N = 779) and 1 year (N = 770) from the CHILD Cohort Study. We identified microbial taxa and co-occurring network clusters associated with asthma and atopy by age 5 years. Genome-wide association studies and gene-by-environment interaction analyses determined main and interaction effects of host genomics and early-life environmental exposures (eg, feeding practices, household pets, and birth characteristics) on gut microbial features.
Shifts in microbial taxa and network clusters during the first year of life were associated with childhood respiratory and atopic outcomes (P < .05), some of which were sex-specific. In addition, some of these implicated microbes were associated with host genomics and early-life exposures. For example, Blautia obeum was associated with reduced food/inhalant sensitization and genetic variants near the MARCO gene (P = 9.4 × 10). Also, variants near the SMAD2 gene interact with breast-feeding to influence the green microbial network cluster (P = 8.3 × 10), associated with asthma.
Our study reports main and interaction effects of genomics and exposures on early-life gut microbiota, which may contribute to childhood asthma and atopy. Improved understanding of the factors contributing to gut dysbiosis will inform on early-life biomarkers and interventions.
肠道微生物群与健康以及儿童疾病（包括哮喘和过敏）的易感性有关。然而，导致肠道微生物群个体差异的基因组因素仍知之甚少。
我们试图将宿主基因组学与生命早期暴露因素相结合，以研究生命第一年对肠道微生物群的主要影响和交互作用。此外，我们还确定了与儿童呼吸道疾病（哮喘、喘息）和特应性疾病（特应性皮炎、食物/吸入性致敏）相关的肠道微生物。
我们利用了儿童队列研究中3个月大（N = 779）和1岁大（N = 770）婴儿粪便的微生物组数据。我们确定了与5岁时哮喘和特应性相关的微生物分类群和共现网络集群。全基因组关联研究和基因-环境交互作用分析确定了宿主基因组学和生命早期环境暴露（如喂养方式、家庭宠物和出生特征）对肠道微生物特征的主要影响和交互作用。
生命第一年微生物分类群和网络集群的变化与儿童呼吸道疾病和特应性疾病相关（P <.05），其中一些具有性别特异性。此外，这些相关微生物中的一些与宿主基因组学和生命早期暴露有关。例如，奥氏布劳特氏菌与食物/吸入性致敏降低以及MARCO基因附近的遗传变异有关（P = 9.4 × 10）。此外，SMAD2基因附近的变异与母乳喂养相互作用，影响与哮喘相关的绿色微生物网络集群（P = 8.3 × 10）。
我们的研究报告了基因组学和暴露因素对生命早期肠道微生物群的主要影响和交互作用，这可能导致儿童哮喘和特应性疾病。对导致肠道微生物群失调的因素有更深入的了解将为生命早期生物标志物和干预措施提供信息。
