宿主遗传、肠道微生物群与美国西班牙裔/拉丁裔成年人哮喘之间的关系
2025/12/30
摘要：
哮喘是一种高度异质性的疾病，常与肥胖共病，并受到多种风险因素的影响。阐明肠道微生物特征与哮喘之间的关联有助于加深我们对其病理生理机制的理解。本研究利用美国西班牙裔/拉丁裔社区健康研究/拉丁裔研究（Hispanic Community Health Study/Study of Latinos）参与者的宿主全基因组测序和粪便鸟枪法宏基因组微生物组数据，探讨宿主遗传和粪便微生物群特征与美国西班牙裔/拉丁裔成年人哮喘之间的关系，同时考虑肥胖状态的影响。我们评估了微生物群特征与哮喘的横断面关联，并分析这些关联是否受肥胖状态（体重指数 ≥30 kg/m²）的调节。我们采用协变量调整的回归分析方法，评估了在不考虑肥胖状态下，α多样性、β多样性及分类丰度与哮喘的差异，以及哮喘与肥胖之间的交互作用。我们还构建了一个哮喘多基因风险评分（polygenic risk score, PRS），并比较了遗传因子与微生物因子对哮喘状态的分类准确性。
结果显示，哮喘与整体分类组成的变化（即β多样性；p = 0.001）有关，而这种变化不依赖于肥胖状态（p = 0.31）。哮喘与α多样性指标无显著相关性（p > 0.17），但肥胖与较低的α多样性相关（p < 0.01）。我们识别出多个与哮喘相关的微生物类群，包括乳酸杆菌属（Lactobacillus）和肠球菌属（Enterococcus）丰度的降低，并且某些分类学关联因肥胖状态而异。与仅包含基线风险因素和哮喘PRS的模型相比，加入微生物信息可提高对哮喘的分类准确性（p = 0.04）。我们的研究结果支持：在美国西班牙裔/拉丁裔成年人中，存在与哮喘相关的微生物群特征，且这种关联独立于肥胖状态。
Relationships among host genetics, gut microbiota, and asthma in US Hispanic/Latino adults
Stanislawski MA, Litkowski E, Arehart CH, Luo K, Gilmore N, Lange LA, Lange EM, Barnes K, Avery CL, Meyer KA, Holguin F, North KE, Burk RD, Kaplan RC
Abstract
Asthma is a heterogeneous condition that is often comorbid with obesity and influenced by diverse risk factors. Elucidating the association of gut microbial characteristics with asthma could improve our understanding of the pathophysiology. Here, we investigate relationships of host genetics and stool microbiota characteristics with asthma among US Hispanic/Latino adults, while considering the influence of obesity status, using host whole genome sequencing and stool shotgun metagenomic microbiota data from participants of the Hispanic Community Health Study/Study of Latinos. We evaluate cross-sectional associations of microbiota characteristics with asthma and analyse whether they are modified by obesity status (body mass index≥30 kg/m2). We assess differences in alpha diversity, beta diversity, and taxonomic abundance with asthma, independent of obesity, and interactions between asthma and obesity using covariate-adjusted regression-based methods. We generate an asthma polygenic risk score (PRS) and compare the classification accuracy of genetic and microbial factors for asthma status. We report that asthma is associated with differences in overall taxonomic composition (beta diversity; p = 0.001), which is not dependent on obesity status (p = 0.31). Asthma is not associated with alpha diversity metrics (p > 0.17), though obesity is associated with lower alpha diversity (p < 0.01). We identify multiple taxa that are associated with asthma, including decreased abundance of Lactobacillus and Enterococcus species, and some taxonomic associations vary by obesity status. Compared to models including baseline risk factors and an asthma PRS, microbial information improves classification accuracy of asthma (p = 0.04). Our results support that there are microbiota characteristics associated with asthma in Hispanic/Latino adults independent of obesity.
哮喘是一种高度异质性的疾病，常与肥胖共病，并受到多种风险因素的影响。阐明肠道微生物特征与哮喘之间的关联有助于加深我们对其病理生理机制的理解。本研究利用美国西班牙裔/拉丁裔社区健康研究/拉丁裔研究（Hispanic Community Health Study/Study of Latinos）参与者的宿主全基因组测序和粪便鸟枪法宏基因组微生物组数据，探讨宿主遗传和粪便微生物群特征与美国西班牙裔/拉丁裔成年人哮喘之间的关系，同时考虑肥胖状态的影响。我们评估了微生物群特征与哮喘的横断面关联，并分析这些关联是否受肥胖状态（体重指数 ≥30 kg/m²）的调节。我们采用协变量调整的回归分析方法，评估了在不考虑肥胖状态下，α多样性、β多样性及分类丰度与哮喘的差异，以及哮喘与肥胖之间的交互作用。我们还构建了一个哮喘多基因风险评分（polygenic risk score, PRS），并比较了遗传因子与微生物因子对哮喘状态的分类准确性。
结果显示，哮喘与整体分类组成的变化（即β多样性；p = 0.001）有关，而这种变化不依赖于肥胖状态（p = 0.31）。哮喘与α多样性指标无显著相关性（p > 0.17），但肥胖与较低的α多样性相关（p < 0.01）。我们识别出多个与哮喘相关的微生物类群，包括乳酸杆菌属（Lactobacillus）和肠球菌属（Enterococcus）丰度的降低，并且某些分类学关联因肥胖状态而异。与仅包含基线风险因素和哮喘PRS的模型相比，加入微生物信息可提高对哮喘的分类准确性（p = 0.04）。我们的研究结果支持：在美国西班牙裔/拉丁裔成年人中，存在与哮喘相关的微生物群特征，且这种关联独立于肥胖状态。
（中日友好医院呼吸与危重症医学科 沈焜路 摘译 林江涛 审校）
（Nat Commun. 2025 Nov 20; DOI: 10.1038/s41467-025-65028-z）
（Nat Commun. 2025 Nov 20; DOI: 10.1038/s41467-025-65028-z）
Relationships among host genetics, gut microbiota, and asthma in US Hispanic/Latino adults
Stanislawski MA, Litkowski E, Arehart CH, Luo K, Gilmore N, Lange LA, Lange EM, Barnes K, Avery CL, Meyer KA, Holguin F, North KE, Burk RD, Kaplan RC
Abstract
Asthma is a heterogeneous condition that is often comorbid with obesity and influenced by diverse risk factors. Elucidating the association of gut microbial characteristics with asthma could improve our understanding of the pathophysiology. Here, we investigate relationships of host genetics and stool microbiota characteristics with asthma among US Hispanic/Latino adults, while considering the influence of obesity status, using host whole genome sequencing and stool shotgun metagenomic microbiota data from participants of the Hispanic Community Health Study/Study of Latinos. We evaluate cross-sectional associations of microbiota characteristics with asthma and analyse whether they are modified by obesity status (body mass index≥30 kg/m2). We assess differences in alpha diversity, beta diversity, and taxonomic abundance with asthma, independent of obesity, and interactions between asthma and obesity using covariate-adjusted regression-based methods. We generate an asthma polygenic risk score (PRS) and compare the classification accuracy of genetic and microbial factors for asthma status. We report that asthma is associated with differences in overall taxonomic composition (beta diversity; p = 0.001), which is not dependent on obesity status (p = 0.31). Asthma is not associated with alpha diversity metrics (p > 0.17), though obesity is associated with lower alpha diversity (p < 0.01). We identify multiple taxa that are associated with asthma, including decreased abundance of Lactobacillus and Enterococcus species, and some taxonomic associations vary by obesity status. Compared to models including baseline risk factors and an asthma PRS, microbial information improves classification accuracy of asthma (p = 0.04). Our results support that there are microbiota characteristics associated with asthma in Hispanic/Latino adults independent of obesity.
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