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儿童肺结核相关下呼吸道微生物组评估。

Assessment of lower respiratory tract microbiota associated with pulmonary tuberculosis in children.

机构信息

Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, Laboratory of Respiratory Diseases, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.

Baoding Hospital of Beijing Children's Hospital, Capital Medical University, Baoding, China.

出版信息

Pediatr Pulmonol. 2024 Dec;59(12):3550-3559. doi: 10.1002/ppul.27253. Epub 2024 Sep 16.

Abstract

BACKGROUND

The respiratory microbiota plays a crucial role in the development of tuberculosis (TB). While existing research has underscored imbalances in the respiratory microbiota of adult patients with TB, information regarding the lower respiratory tract (LRT) microbiota in pediatric patients with TB remains scarce.

METHODS

We employed 16S rRNA gene sequencing technology to investigate the LRT microbial communities of 85 children of different ages with active TB of different severities, 33 children with infectious diseases other than TB, and 48 sex- and age-matched healthy children.

RESULTS

A marked imbalance in the respiratory microbiota was observed in children with TB, highlighted by reduced alpha diversity and a distinct microbial community structure. Comparative analysis indicated that patients with severe TB exhibited lower Neisseria levels than those with non-severe TB (1.01% vs. 3.93%, respectively; p = .02). Streptococcus and Gemella levels were lower in bacteriologically confirmed TB cases compared with clinically diagnosed cases, and higher in healthy children younger than 10 years old than in the older group. Spearman correlation analysis demonstrated significant associations between the microbiota of the LRT and cytokine concentrations in the sputum of children with TB (e.g., an inverse correlation between Veillonella and interleukin-17A).

CONCLUSIONS

TB induced significant dysbiosis in the LRT microbiota of children that was associated with disease severity and the immunological response in the respiratory tract. Our findings may offer a deeper understanding of the role of the respiratory microbiome in TB pathogenesis and progression.

摘要

背景

呼吸道微生物群在结核病(TB)的发展中起着至关重要的作用。虽然现有研究强调了成人 TB 患者呼吸道微生物群的失衡,但关于儿童 TB 患者下呼吸道(LRT)微生物群的信息仍然很少。

方法

我们使用 16S rRNA 基因测序技术,调查了 85 名不同年龄、不同严重程度的活动性 TB 儿童、33 名患有非 TB 传染病的儿童和 48 名性别和年龄匹配的健康儿童的 LRT 微生物群落。

结果

TB 患儿的呼吸道微生物群明显失衡,表现在 alpha 多样性降低和微生物群落结构明显不同。比较分析表明,严重 TB 患者的奈瑟菌水平低于非严重 TB 患者(分别为 1.01%和 3.93%;p = 0.02)。与临床诊断病例相比,细菌学确诊的 TB 病例中链球菌和杰氏菌水平较低,而 10 岁以下的健康儿童高于年龄较大的儿童。Spearman 相关分析表明,TB 患儿 LRT 微生物群与痰液细胞因子浓度之间存在显著相关性(例如,韦荣球菌与白细胞介素-17A 呈负相关)。

结论

TB 导致儿童 LRT 微生物群发生显著失调,与疾病严重程度和呼吸道免疫反应有关。我们的发现可能加深了对呼吸道微生物组在 TB 发病机制和进展中的作用的理解。

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