Department of Medical Microbiology, Capital Medical University, Beijing, China.
Department of Respiratory Medicine, Beijing Children's Hospital, Beijing, China.
Pediatr Allergy Immunol. 2020 Apr;31(3):281-289. doi: 10.1111/pai.13183. Epub 2020 Jan 22.
Early interactions between respiratory viruses and microbiota might modulate host immune responses and subsequently contribute to later development of recurrent wheezing and asthma in childhood. We aimed to study the possible association between respiratory microbiome, host immune response, and the development of recurrent wheezing in infants with severe respiratory syncytial virus (RSV) bronchiolitis.
Seventy-four infants who were hospitalized at Beijing Children's Hospital during an initial episode of severe RSV bronchiolitis at 6 months of age or less were included and followed up until the age of 3 years. Sputum samples were collected, and their microbiota profiles, LPS, and cytokines were analyzed by 16S rRNA-based sequencing, ELISA, and multiplex immunoassay, respectively.
Twenty-six (35.1%) infants developed recurrent wheezing by the age of 3 years, and 48 (64.9%) did not. The relative abundance of Haemophilus, Moraxella, and Klebsiella was higher in infants who later developed recurrent wheezing than in those who did not (LDA score >3.5). Airway levels of LPS (P = .003), CXCL8 (P = .004), CCL5 (P = .029), IL-6 (P = .004), and IL-13 (P < .001) were significantly higher in infants who later developed recurrent wheezing than in those who did not. Moreover, high airway abundance of Haemophilus was associated with CXCL8 (r = 0.246, P = .037) level, and that of Moraxella was associated with IL-6 level (r = 0.236, P = .046) and IL-10 level (r = 0.266, P = .024).
Our study suggests that higher abundance of Haemophilus and Moraxella in airway microbiome might modulate airway inflammation during severe RSV bronchiolitis in infancy, potentially contributing to the development of subsequent recurrent wheezing in later childhood.
呼吸道病毒和微生物组的早期相互作用可能调节宿主免疫反应，并随后导致儿童反复喘息和哮喘的发展。我们旨在研究呼吸道微生物组、宿主免疫反应与严重呼吸道合胞病毒（RSV）毛细支气管炎婴儿反复喘息发展之间的可能关联。
74 名婴儿在 6 个月龄或以下因严重 RSV 毛细支气管炎初次住院，一直随访至 3 岁。收集痰液样本，通过 16S rRNA 测序、ELISA 和多重免疫分析分别分析其微生物组谱、内毒素（LPS）和细胞因子。
26 名（35.1%）婴儿在 3 岁时发展为反复喘息，48 名（64.9%）未发展为反复喘息。与未发展为反复喘息的婴儿相比，后来发展为反复喘息的婴儿中嗜血杆菌、莫拉菌和克雷伯菌的相对丰度更高（LDA 评分>3.5）。后来发展为反复喘息的婴儿气道 LPS（P=0.003）、CXCL8（P=0.004）、CCL5（P=0.029）、IL-6（P=0.004）和 IL-13（P<0.001）水平明显更高。此外，气道中嗜血杆菌的高丰度与 CXCL8 水平（r=0.246，P=0.037）相关，而莫拉菌与 IL-6 水平（r=0.236，P=0.046）和 IL-10 水平（r=0.266，P=0.024）相关。
我们的研究表明，呼吸道微生物组中嗜血杆菌和莫拉菌的丰度增加可能调节婴儿严重 RSV 毛细支气管炎期间的气道炎症，从而可能导致以后儿童期反复喘息的发展。
