哮喘治疗的精准医学：释放表观基因组和微生物组的潜力
2024/06/26
摘要
哮喘是一项全球主要的生物医学问题。患者可能会出现危及生命的发作(加重)，通常通过抗炎和支气管舒张剂控制发作。然而，在治疗应答方面存在明显的异质性，一部分未缓解的哮喘患者承担了该病的主要负担。表观基因组和微生物组的研究可能弥合人类遗传学和环境暴露之间的鸿沟，部分解释药物应答的异质性。本综述旨在对微生物组和表观遗传学研究与哮喘治疗和药物反应之间的关联进行批判性审查，强调聚合途径，解决当前的挑战，并提出未来的展望。目前的表观遗传学和微生物组学研究表明，哮喘药物干预与人类表观基因组和微生物组之间存在双边关系。这些研究集中在皮质类固醇，其次是支气管舒张剂、阿奇霉素、免疫疗法和美泊利单抗，这些研究提高了对治疗应答的分子基础的理解，并确定了有前景的药物应答预测生物标志物。免疫和炎症通路(即IL-2、TNF-α、NF-κB和cebp)是与哮喘治疗相关的微生物组-表观遗传关联的基础，代表了潜在的靶向治疗途径。对这些组学生物标志物的全面评估将有助于精准医疗和新治疗靶点的发现。
Precision Medicine for Asthma Treatment: Unlocking the Potential of the Epigenome and Microbiome
Javier Perez-Garcia, Andres Cardenas, Fabian Lorenzo-Diaz, Maria Pino-Yanes
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 exposures 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 pharmacological 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 (i.e., IL-2, TNF-α, NF-κB, and CEBPs) underlie microbiome-epigenetic associations with asthma treatment, representing potential therapeutic pathways to be targeted. A comprehensive evaluation of these omic biomarkers could significantly contribute to precision medicine and new therapeutic target discovery.
哮喘是一项全球主要的生物医学问题。患者可能会出现危及生命的发作(加重)，通常通过抗炎和支气管舒张剂控制发作。然而，在治疗应答方面存在明显的异质性，一部分未缓解的哮喘患者承担了该病的主要负担。表观基因组和微生物组的研究可能弥合人类遗传学和环境暴露之间的鸿沟，部分解释药物应答的异质性。本综述旨在对微生物组和表观遗传学研究与哮喘治疗和药物反应之间的关联进行批判性审查，强调聚合途径，解决当前的挑战，并提出未来的展望。目前的表观遗传学和微生物组学研究表明，哮喘药物干预与人类表观基因组和微生物组之间存在双边关系。这些研究集中在皮质类固醇，其次是支气管舒张剂、阿奇霉素、免疫疗法和美泊利单抗，这些研究提高了对治疗应答的分子基础的理解，并确定了有前景的药物应答预测生物标志物。免疫和炎症通路(即IL-2、TNF-α、NF-κB和cebp)是与哮喘治疗相关的微生物组-表观遗传关联的基础，代表了潜在的靶向治疗途径。对这些组学生物标志物的全面评估将有助于精准医疗和新治疗靶点的发现。
(中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校)
(J Allergy Clin Immunol. 2024 Jun 19:S0091-6749(24)00634-1. doi: 10.1016/j.jaci.2024.06.010.)
(J Allergy Clin Immunol. 2024 Jun 19:S0091-6749(24)00634-1. doi: 10.1016/j.jaci.2024.06.010.)
Precision Medicine for Asthma Treatment: Unlocking the Potential of the Epigenome and Microbiome
Javier Perez-Garcia, Andres Cardenas, Fabian Lorenzo-Diaz, Maria Pino-Yanes
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 exposures 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 pharmacological 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 (i.e., IL-2, TNF-α, NF-κB, and CEBPs) underlie microbiome-epigenetic associations with asthma treatment, representing potential therapeutic pathways to be targeted. A comprehensive evaluation of these omic biomarkers could significantly contribute to precision medicine and new therapeutic target discovery.
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重度哮喘患者对omalizumab、benralizumab和mepolizumab完全缓解者与非完全缓解者的临床特征:
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加味阳和汤通过抑制2组固有淋巴细胞反应减轻过敏性气道炎症
