Stool and Airway Microbiome Signatures Associated With Treatment Response to Dupilumab in Severe Asthma: Findings From the PRISM Study

IF 11.3 1区医学 Q1 ALLERGY

Allergy Pub Date : 2026-09-23 DOI:10.1111/all.70524

Ga‐Eun Yie, Eunse Kim, Duong Duc Pham, Chae Eun Lee, Heui Song, Yoon‐Keun Kim, Chil‐Sung Kang, Hyouk‐Soo Kwon, Woo‐Jung Song, You Sook Cho, Sei Won Lee, Ga‐Young Ban, Taehoon Lee, Min‐Hye Kim, Kyung‐Min Ahn, Sang Min Lee, Pankaj K. Bhavsar, Ian M. Adcock, Kian Fan Chung, Sungho Won, Tae‐Bum Kim

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引用次数: 0

Abstract

Background Severe asthma is characterized by persistent airway inflammation and heterogeneous responses to biologic therapies. Growing evidence implicates the gut–lung axis in asthma pathophysiology; however, few studies have concurrently characterized gut and airway microbiomes in relation to treatment response in severe asthma. Methods We profiled microbiomes of stool bacteria (STB), stool‐derived extracellular vesicles (STE), and exhaled breath condensate (EBC) from 48 patients with severe asthma receiving dupilumab. Microbial composition, alpha diversity, and predicted functional profiles were compared across sample types and longitudinally according to treatment response. Associations between microbial features and asthma‐related clinical markers were also evaluated. Results Distinct taxonomic and predicted functional signatures were identified across biological compartments. EBC samples were enriched in Proteobacteria, including Pseudomonas , and exhibited a higher predicted abundance of pathways related to two‐component systems and bacterial secretion systems. EBC microbial diversity was positively associated with baseline sputum eosinophil levels ( p = 0.018), whereas stool microbial richness demonstrated a time‐dependent association with blood eosinophil counts after treatment ( p for interaction = 0.023). Treatment responders exhibited lower abundances of Lachnospira (STB q = 0.046; STE q = 0.042) and Escherichia–Shigella (STE q = 0.038), and a higher relative abundance of the Oscillospiraceae NK4A214 group (STB q = 5.5 × 10 −7 , STE q = 1.4 × 10 −8 ) in stool‐derived profiles. Conclusion Gut and airway‐derived microbiomes appear to play complementary roles in severe asthma. Stool‐derived microbial features may reflect systemic inflammatory signals associated with treatment response, whereas airway‐derived microbial profiles reflect local airway inflammation. Integrating multi‐compartment microbiome data may improve the understanding of heterogeneity in biologic treatment response among patients with severe asthma.

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重度哮喘患者对Dupilumab的治疗反应与粪便和气道微生物组特征相关：PRISM研究结果

重度哮喘的特点是持续的气道炎症和对生物治疗的不均匀反应。越来越多的证据表明，肠-肺轴参与哮喘病理生理；然而，很少有研究同时描述了肠道和气道微生物组与严重哮喘治疗反应的关系。方法：我们分析了48例接受dupilumab治疗的严重哮喘患者的粪便细菌（STB）、粪便来源的细胞外囊泡（STE）和呼气冷凝水（EBC）的微生物组。微生物组成、α多样性和预测的功能谱在不同的样品类型之间进行比较，并根据处理反应纵向进行比较。还评估了微生物特征与哮喘相关临床标志物之间的关系。结果在不同的生物区室中鉴定出不同的分类和预测功能特征。EBC样品富含变形菌，包括假单胞菌，并显示出更高的预测丰度，与双组分系统和细菌分泌系统相关的途径。EBC微生物多样性与基线痰嗜酸性粒细胞水平呈正相关（p = 0.018），而粪便微生物丰富度与治疗后血液嗜酸性粒细胞计数呈时间依赖性相关（相互作用p = 0.023）。治疗应答者在粪便来源谱中表现出较低的毛螺旋体（STB q = 0.046; STE q = 0.042）和埃希菌-志贺氏菌（STE q = 0.038）丰度，而Oscillospiraceae NK4A214组（STB q = 5.5 × 10−7,STE q = 1.4 × 10−8）的相对丰度较高。结论肠道和气道来源的微生物群在严重哮喘中起互补作用。粪便来源的微生物特征可能反映与治疗反应相关的全身炎症信号，而气道来源的微生物特征反映局部气道炎症。整合多区室微生物组数据可以提高对重症哮喘患者生物治疗反应异质性的理解。

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来源期刊

Allergy 医学-过敏

CiteScore

26.10

自引率

9.70%

发文量

393

审稿时长

2 months

期刊介绍： Allergy is an international and multidisciplinary journal that aims to advance, impact, and communicate all aspects of the discipline of Allergy/Immunology. It publishes original articles, reviews, position papers, guidelines, editorials, news and commentaries, letters to the editors, and correspondences. The journal accepts articles based on their scientific merit and quality. Allergy seeks to maintain contact between basic and clinical Allergy/Immunology and encourages contributions from contributors and readers from all countries. In addition to its publication, Allergy also provides abstracting and indexing information. Some of the databases that include Allergy abstracts are Abstracts on Hygiene & Communicable Disease, Academic Search Alumni Edition, AgBiotech News & Information, AGRICOLA Database, Biological Abstracts, PubMed Dietary Supplement Subset, and Global Health, among others.