Abstract：
Asthma is a leading worldwide biomedical concern. Patients can experience life-threatening worsening episodes (exacerbations) usually controlled by anti-inflammatory and bronchodilator drugs. However, substantial heterogeneity in treatment response exists, and a subset of patients with unresolved asthma carry the major burden of this disease. The study of the epigenome and microbiome might bridge the gap between human genetics and environmental exposure to partially explain the heterogeneity in drug response. This review aims to provide a critical examination of the existing literature on the microbiome and epigenetic studies examining associations with asthma treatments and drug response, highlight convergent pathways, address current challenges, and offer future perspectives. Current epigenetic and microbiome studies have shown the bilateral relationship between asthma pharmacologic interventions and the human epigenome and microbiome. These studies, focusing on corticosteroids and to a lesser extent on bronchodilators, azithromycin, immunotherapy, and mepolizumab, have improved the understanding of the molecular basis of treatment response and identified promising biomarkers for drug response prediction. Immune and inflammatory pathways (eg, IL-2, TNF-α, NF-κB, and C/EBPs) underlie microbiome-epigenetic associations with asthma treatment, representing potential therapeutic pathways to be targeted. A comprehensive evaluation of these omics biomarkers could significantly contribute to precision medicine and new therapeutic target discovery.
摘要：
哮喘是全球领先的生物医学问题。患者可经历通常由抗炎和支气管扩张剂药物控制的危及生命的恶化发作(恶化)。然而,治疗反应存在显著异质性,一部分未解决的哮喘患者承担着该疾病的主要负担.表观基因组和微生物组的研究可能会弥合人类遗传学和环境暴露之间的差距，以部分解释药物反应的异质性。这篇综述旨在对现有的微生物组和表观遗传学研究文献进行严格审查，以检查与哮喘治疗和药物反应的关联。突出聚合路径，应对当前的挑战，并提供未来的前景。目前的表观遗传学和微生物组研究表明，哮喘药物干预与人类表观基因组和微生物组之间存在双向关系。这些研究,专注于皮质类固醇和较小程度的支气管扩张剂，阿奇霉素,免疫疗法，和美泊利单抗，提高了对治疗反应的分子基础的理解，并确定了有希望的生物标志物用于药物反应预测。免疫和炎症途径(即，IL-2,TNF-α,NF-κB,和CEBP）是与哮喘治疗有关的微生物组-表观遗传关联的基础，代表潜在的靶向治疗途径。对这些生物标志物的综合评估可以显着有助于精准医学和新的治疗靶标的发现。
