关键词: Haemophilus IgA IgM Pneumococcus chronic obstructive pulmonary disease common variable immunodeficiency microbiome and dysbiosis oropharyngeal microbiome

Mesh : Humans Common Variable Immunodeficiency / microbiology immunology complications Oropharynx / microbiology Male Female Middle Aged Adult Respiratory Tract Infections / microbiology immunology Dysbiosis Microbiota Prospective Studies Aged RNA, Ribosomal, 16S / genetics Acute Disease Bacteria / classification genetics Case-Control Studies

来  源:   DOI:10.3389/fimmu.2024.1371118   PDF(Pubmed)

Abstract:
UNASSIGNED: The respiratory tract microbiome is essential for human health and well-being and is determined by genetic, lifestyle, and environmental factors. Patients with Common Variable Immunodeficiency (CVID) suffer from respiratory and intestinal tract infections, leading to chronic diseases and increased mortality rates. While CVID patients\' gut microbiota have been analyzed, data on the respiratory microbiome ecosystem are limited.
UNASSIGNED: This study aims to analyze the bacterial composition of the oropharynx of adults with CVID and its link with clinical and immunological features and risk for respiratory acute infections.
UNASSIGNED: Oropharyngeal samples from 72 CVID adults and 26 controls were collected in a 12-month prospective study. The samples were analyzed by metagenomic bacterial 16S ribosomal RNA sequencing and processed using the Quantitative Insights Into Microbial Ecology (QIME) pipeline. Differentially abundant species were identified and used to build a dysbiosis index. A machine learning model trained on microbial abundance data was used to test the power of microbiome alterations to distinguish between healthy individuals and CVID patients.
UNASSIGNED: Compared to controls, the oropharyngeal microbiome of CVID patients showed lower alpha- and beta-diversity, with a relatively increased abundance of the order Lactobacillales, including the family Streptococcaceae. Intra-CVID analysis identified age >45 years, COPD, lack of IgA, and low residual IgM as associated with a reduced alpha diversity. Expansion of Haemophilus and Streptococcus genera was observed in patients with undetectable IgA and COPD, independent from recent antibiotic use. Patients receiving azithromycin as antibiotic prophylaxis had a higher dysbiosis score. Expansion of Haemophilus and Anoxybacillus was associated with acute respiratory infections within six months.
UNASSIGNED: CVID patients showed a perturbed oropharynx microbiota enriched with potentially pathogenic bacteria and decreased protective species. Low residual levels of IgA/IgM, chronic lung damage, anti antibiotic prophylaxis contributed to respiratory dysbiosis.
摘要:
呼吸道微生物群对人类健康和福祉至关重要,由遗传决定,生活方式,和环境因素。常见可变免疫缺陷(CVID)患者患有呼吸道和肠道感染,导致慢性疾病和死亡率上升。虽然已经分析了CVID患者的肠道微生物群,关于呼吸微生物组生态系统的数据是有限的。
本研究旨在分析患有CVID的成年人口咽的细菌组成及其与临床和免疫学特征的联系以及呼吸道急性感染的风险。
在一项为期12个月的前瞻性研究中,收集了72名CVID成年人和26名对照的口咽样本。通过宏基因组细菌16S核糖体RNA测序分析样品,并使用进入微生物生态学的定量洞察(QIME)流水线进行处理。鉴定了差异丰富的物种,并将其用于建立菌群失调指数。使用在微生物丰度数据上训练的机器学习模型来测试微生物组改变区分健康个体和CVID患者的能力。
与对照组相比,CVID患者的口咽微生物组显示较低的α-和β-多样性,乳杆菌的丰度相对增加,包括链球菌科。CVID内分析确定年龄>45岁,COPD,缺乏IgA,和低残留IgM与α多样性降低相关。在检测不到IgA和COPD的患者中观察到嗜血杆菌和链球菌属的扩增,独立于最近的抗生素使用。接受阿奇霉素作为抗生素预防的患者的菌群失调评分较高。嗜血杆菌和厌氧菌的扩张与6个月内的急性呼吸道感染有关。
CVID患者显示出富含潜在致病细菌和保护性物种减少的口咽微生物群。低残留水平的IgA/IgM,慢性肺损伤,预防抗抗生素可导致呼吸道菌群失调。
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