哮喘患者与对照者的气道微生物组多样性、粘膜内细菌及空间免疫
2026/06/01
摘要
背景 ：哮喘的特征是胸腔气道粘膜破坏以及微生物多样性丧失。对粘膜转录组进行空间分析，可能系统性地揭示微生物影响免疫的机制。
目的：我们旨在探究有或无哮喘受试者支气管活检组织不同分层中的临床指标、微生物群落与宿主粘膜转录组之间的关系。
方法：我们对 65 名成年哮喘患者和 44 名健康对照者进行了支气管镜检查，通过 16S rRNA 基因扩增子序列对支气管刷检样本中的细菌操作分类单元（OTU）进行定量。在不了解诊断的情况下对活检组织的组织学特征进行盲法评分。对 44 份活检组织进行 16S rRNA 原位杂交后，对上皮、基底膜和间质中的细菌聚集灶进行评分。利用数字空间分析技术对上皮和间质区室的全球人类基因表达进行定量。
结果 ：临床哮喘的独立预测因素包括基底膜异常（BaseMA）、支气管内细菌多样性以及循环嗜酸性粒细胞计数，而非特定 OTU 的丰度。16S rRNA 染色显示，所有活检组织的上皮和粘膜内均存在细菌。粘膜内细菌（IMCB）计数与编码抗原特异性免疫、中性粒细胞功能和基质活化的空间组织共表达网络呈负相关，而基底膜异常则与适应性免疫模块呈正相关。嗜酸性粒细胞计数与上皮细菌计数及衰老通路相关。临床哮喘伴随调节性 T 细胞（Treg）网络的上调。
结论：哮喘及其相关表型伴随复杂的粘膜事件，这些事件超出了嗜酸性粒细胞通路的范畴。多样化气道微生物群的组分可能通过粘膜内的有益相互作用来调节免疫。
Airway microbiome diversity, intra-mucosal bacteria, and spatial immunity in asthmatics and controls
Moffatt MF, Nishimura T, Cox MJ, et al.
Abstract
BACKGROUND:Asthma is characterized by disruption of the thoracic airway mucosae and loss of microbial diversity. Spatial profiling of the mucosal transcriptome may systematically discover mechanisms for microbial influences on immunity.
OBJECTIVES:We investigated relationships between clinical measures, microbial communities, and the host mucosal transcriptome within different strata of bronchial biopsies in subjects with and without asthma.
METHODS:We bronchoscoped 65 adult asthmatics and 44 healthy controls, quantifying bacterial operational taxonomic units (OTUs) in bronchial brushings by 16S rRNA gene amplicon sequences. Biopsy histologic features were scored blind to diagnosis. Following 16S rRNA in situ hybridization of 44 biopsies, bacterial foci were scored in epithelium, basement membrane and stroma. Global human gene expression was quantified in epithelial and stromal compartments using Digital Spatial Profiling.
RESULTS:Clinical asthma was independently predicted by basement membrane abnormalities (BaseMA), endobronchial bacterial diversity and circulating eosinophil counts, but not by specific OTU abundances. 16S rRNA staining revealed bacteria within epithelium and mucosa of all biopsies. Intra-mucosal bacteria (IMCBs) counts correlated negatively with spatially organized co-expression networks encoding antigen-specific immunity, neutrophil functions, and matrix activation, whereas BaseMA correlated positively with the adaptive immunity module. Eosinophil counts correlated with epithelial bacterial counts and senescence pathways. Clinical asthma was accompanied by upregulation of a Treg cell network.
CONCLUSIONS:Asthma and its related phenotypes are accompanied by complex mucosal events that extend beyond eosinophilic pathways. Components of diverse airway microbiota may modify immunity by beneficial interactions within the mucosa.
背景 ：哮喘的特征是胸腔气道粘膜破坏以及微生物多样性丧失。对粘膜转录组进行空间分析，可能系统性地揭示微生物影响免疫的机制。
目的：我们旨在探究有或无哮喘受试者支气管活检组织不同分层中的临床指标、微生物群落与宿主粘膜转录组之间的关系。
方法：我们对 65 名成年哮喘患者和 44 名健康对照者进行了支气管镜检查，通过 16S rRNA 基因扩增子序列对支气管刷检样本中的细菌操作分类单元（OTU）进行定量。在不了解诊断的情况下对活检组织的组织学特征进行盲法评分。对 44 份活检组织进行 16S rRNA 原位杂交后，对上皮、基底膜和间质中的细菌聚集灶进行评分。利用数字空间分析技术对上皮和间质区室的全球人类基因表达进行定量。
结果 ：临床哮喘的独立预测因素包括基底膜异常（BaseMA）、支气管内细菌多样性以及循环嗜酸性粒细胞计数，而非特定 OTU 的丰度。16S rRNA 染色显示，所有活检组织的上皮和粘膜内均存在细菌。粘膜内细菌（IMCB）计数与编码抗原特异性免疫、中性粒细胞功能和基质活化的空间组织共表达网络呈负相关，而基底膜异常则与适应性免疫模块呈正相关。嗜酸性粒细胞计数与上皮细菌计数及衰老通路相关。临床哮喘伴随调节性 T 细胞（Treg）网络的上调。
结论：哮喘及其相关表型伴随复杂的粘膜事件，这些事件超出了嗜酸性粒细胞通路的范畴。多样化气道微生物群的组分可能通过粘膜内的有益相互作用来调节免疫。
（中日友好医院呼吸与危重症医学科 李春晓 摘译 林江涛 审校）
（Am J Respir Crit Care Med. 2026 May 9:aamag232.DOI: 10.1093/ajrccm/aamag232.）
（Am J Respir Crit Care Med. 2026 May 9:aamag232.DOI: 10.1093/ajrccm/aamag232.）
Airway microbiome diversity, intra-mucosal bacteria, and spatial immunity in asthmatics and controls
Moffatt MF, Nishimura T, Cox MJ, et al.
Abstract
BACKGROUND:Asthma is characterized by disruption of the thoracic airway mucosae and loss of microbial diversity. Spatial profiling of the mucosal transcriptome may systematically discover mechanisms for microbial influences on immunity.
OBJECTIVES:We investigated relationships between clinical measures, microbial communities, and the host mucosal transcriptome within different strata of bronchial biopsies in subjects with and without asthma.
METHODS:We bronchoscoped 65 adult asthmatics and 44 healthy controls, quantifying bacterial operational taxonomic units (OTUs) in bronchial brushings by 16S rRNA gene amplicon sequences. Biopsy histologic features were scored blind to diagnosis. Following 16S rRNA in situ hybridization of 44 biopsies, bacterial foci were scored in epithelium, basement membrane and stroma. Global human gene expression was quantified in epithelial and stromal compartments using Digital Spatial Profiling.
RESULTS:Clinical asthma was independently predicted by basement membrane abnormalities (BaseMA), endobronchial bacterial diversity and circulating eosinophil counts, but not by specific OTU abundances. 16S rRNA staining revealed bacteria within epithelium and mucosa of all biopsies. Intra-mucosal bacteria (IMCBs) counts correlated negatively with spatially organized co-expression networks encoding antigen-specific immunity, neutrophil functions, and matrix activation, whereas BaseMA correlated positively with the adaptive immunity module. Eosinophil counts correlated with epithelial bacterial counts and senescence pathways. Clinical asthma was accompanied by upregulation of a Treg cell network.
CONCLUSIONS:Asthma and its related phenotypes are accompanied by complex mucosal events that extend beyond eosinophilic pathways. Components of diverse airway microbiota may modify immunity by beneficial interactions within the mucosa.
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