Objective: This study aimed to investigate the gut microbiome profile in different inflammatory phenotypes of treatment-naive newly diagnosed asthmatic adults, to gain insight on the associations between intestinal microbiota and phenotypic features that characterize asthma heterogeneity to develop new treatments for asthma.
Methods: Fresh stool samples were obtained from 20 healthy subjects and 47 newly diagnosed asthmatic patients prior to any interventions. The asthmatics were divided into allergic and non-allergic cohorts. Intestinal microbiota was analyzed by 16S rRNA next-generation sequencing. Demographic and clinical parameters were collected. Alpha and beta diversity analysis were calculated to detect differences within sample phylotype richness and evenness between controls and asthmatic patients. Statistically significant differences between samples were analyzed for all used metrics, and features of gut bacterial community structure were evaluated in relation to extensive clinical characteristics of asthmatic patients.
Results: Gut microbial compositions were significantly different between asthmatic and healthy groups. Alpha-diversity of the gut microbiome was significantly lower in asthmatics than in controls. The microbiome between allergic and non-allergic asthmatic patients were also different, and 28 differential species were identified. PPAR signaling pathway, carotenoid biosynthesis, and flavonoid biosynthesis were significantly positively correlated with allergy-associated clinical index, including FENO value, blood eosinophil counts, and serum IgE and IL-4 levels. A combination of Ruminococcus bromii, Brevundimonas vesicularis, and Clostridium disporicum showed an AUC of 0.743 in the specific allergic/non-allergic cohort. When integrating C. disporicum, flavone, flavonol biosynthesis, and serum IL-4 values, the AUC achieved 0.929 to classify asthmatics. At the same time, C. colinum and its associated functional pathway exhibited an AUC of 0.78 to distinguish allergic asthmatics from those without allergies.
Conclusion: We demonstrated a distinct taxonomic composition of gut microbiota in different asthmatic phenotypes, highlighting their significant relationships. Our study may support considerations of intestinal microbial signatures in delineating asthma phenotypes.

Keywords: asthma, phenotypes, gut microbiota, 16S rRNA next-generation sequencing, functional pathway


中文翻译：

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肠道菌群与哮喘内型之间的关联：基于新诊断哮喘患者的华南地区横断面研究

目的：本研究旨在调查未接受治疗的新诊断哮喘成人不同炎症表型中的肠道微生物组谱，以深入了解肠道微生物群与表征哮喘异质性的表型特征之间的关联，从而开发出新的哮喘治疗方法。
方法：在任何干预之前，从 20 名健康受试者和 47 名新诊断的哮喘患者中获取新鲜粪便样本。哮喘患者被分为过敏组和非过敏组。通过 16S rRNA 二代测序分析肠道微生物群。收集人口统计学和临床​​参数。计算 Alpha 和 Beta 多样性分析以检测对照组和哮喘患者之间样本系统型丰富度和均匀度的差异。对所有使用的指标分析样本之间的统计学显着差异，并根据哮喘患者的广泛临床特征评估肠道细菌群落结构的特征。
结果：哮喘组和健康组的肠道微生物组成存在显着差异。哮喘患者肠道微生物群的α多样性显着低于对照组。过敏性和非过敏性哮喘患者之间的微生物组也不同，共鉴定出 28 个不同的物种。PPAR信号通路、类胡萝卜素生物合成和类黄酮生物合成与过敏相关临床指标，包括FENO值、血嗜酸性粒细胞计数、血清IgE和IL-4水平呈显着正相关。在特定的过敏/非过敏队列中，溴化瘤胃球菌、囊泡短单胞菌和梭状芽孢杆菌的组合显示 AUC 为 0.743。当整合C. disporicum、黄酮、黄酮醇的生物合成和血清 IL-4 值，AUC 达到 0.929 来对哮喘患者进行分类。同时，大肠杆菌及其相关功能通路的 AUC 为 0.78，可以区分过敏性哮喘患者和非过敏性哮喘患者。
结论：我们展示了不同哮喘表型中肠道微生物群的独特分类组成，突出了它们之间的重要关系。我们的研究可能支持在描述哮喘表型时考虑肠道微生物特征。

关键词：哮喘，表型，肠道菌群，16S rRNA二代测序，功能通路