Perez-Garcia Javier, González-Carracedo Mario, Espuela-Ortiz Antonio, Hernández-Pérez José M, González-Pérez Ruperto, Sardón-Prado Olaia, Martin-Gonzalez Elena, Mederos-Luis Elena, Poza-Guedes Paloma, Corcuera-Elosegui Paula, Callero Ariel, Sánchez-Machín Inmaculada, Korta-Murua Javier, Pérez-Pérez José A, Villar Jesús, Pino-Yanes Maria, Lorenzo-Diaz Fabian
Genomics and Health Group, Department of Biochemistry, Microbiology, Cell Biology and Genetics, Universidad de La Laguna (ULL), La Laguna, Tenerife, Spain.
Department of Biochemistry, Microbiology, Cell Biology and Genetics, ULL, La Laguna, Tenerife, Spain; Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), ULL, La Laguna, Tenerife, Spain.
J Allergy Clin Immunol. 2023 Mar;151(3):706-715. doi: 10.1016/j.jaci.2022.09.041. Epub 2022 Nov 4.
The response to inhaled corticosteroids (ICS) in asthma is affected by the interplay of several factors. Among these, the role of the upper-airway microbiome has been scarcely investigated. We aimed to evaluate the association between the salivary, pharyngeal, and nasal microbiome with asthma exacerbations despite receipt of ICS.
Samples from 250 asthma patients from the Genomics and Metagenomics of Asthma Severity (GEMAS) study treated with ICS were analyzed. Control/case subjects were defined by the absence/presence of asthma exacerbations in the past 6 months despite being treated with ICS. The bacterial microbiota was profiled by sequencing the V3-V4 region of the 16S rRNA gene. Differences between groups were assessed by PERMANOVA and regression models adjusted for potential confounders. A false discovery rate (FDR) of 5% was used to correct for multiple comparisons. Classification models of asthma exacerbations despite ICS treatment were built with machine learning approaches based on clinical, genetic, and microbiome data.
In nasal and saliva samples, case subjects had lower bacterial diversity (Richness, Shannon, and Faith indices) than control subjects (.007 ≤ P ≤ .037). Asthma exacerbations accounted for 8% to 9% of the interindividual variation of the salivary and nasal microbiomes (.003 ≤ P ≤ .046). Three, 4, and 11 bacterial genera from the salivary, pharyngeal, and nasal microbiomes were differentially abundant between groups (4.09 × 10 ≤ FDR ≤ 0.047). Integrating clinical, genetic, and microbiome data showed good discrimination for the development of asthma exacerbations despite receipt of ICS (AUC: 0.82 and AUC: 0.77).
The diversity and composition of the upper-airway microbiome are associated with asthma exacerbations despite ICS treatment. The salivary microbiome has a potential application as a biomarker of asthma exacerbations despite receipt of ICS.
哮喘患者对吸入性糖皮质激素（ICS）的反应受多种因素相互作用的影响。其中，上呼吸道微生物群的作用鲜有研究。我们旨在评估唾液、咽部和鼻腔微生物群与尽管接受ICS治疗但仍发生哮喘急性加重之间的关联。
对哮喘严重程度的基因组学和宏基因组学（GEMAS）研究中250例接受ICS治疗的哮喘患者的样本进行分析。根据过去6个月内尽管接受ICS治疗但有无哮喘急性加重来定义对照/病例组。通过对16S rRNA基因的V3-V4区域进行测序来分析细菌微生物群。采用PERMANOVA和针对潜在混杂因素进行调整的回归模型评估组间差异。采用5%的错误发现率（FDR）校正多重比较。基于临床、遗传和微生物组数据，采用机器学习方法建立尽管接受ICS治疗但仍发生哮喘急性加重的分类模型。
在鼻腔和唾液样本中，病例组的细菌多样性（丰富度、香农指数和费思指数）低于对照组（0.007≤P≤0.037）。哮喘急性加重占唾液和鼻腔微生物群个体间变异的8%至9%（0.003≤P≤0.046）。唾液、咽部和鼻腔微生物群中分别有3个、4个和11个细菌属在组间差异丰富（4.09×10≤FDR≤0.047）。整合临床、遗传和微生物组数据显示，尽管接受ICS治疗，但对哮喘急性加重的发生具有良好的辨别能力（AUC：0.82和AUC：0.77）。
尽管接受ICS治疗，但上呼吸道微生物群的多样性和组成与哮喘急性加重相关。唾液微生物群有可能作为尽管接受ICS治疗但仍发生哮喘急性加重的生物标志物。
