Whole Genome Shotgun Sequencing on Nasopharyngeal microbiome in Hong Kong Pre-school Children with Asthma Exacerbations
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摘要Background: Asthma exacerbation (AE) exerts heavy burden on society. Microbiome is an important driver for the development of immune-mediated diseases, but very few studies looked at microbiome during AE. There was limited whole genome shotgun (WGS) sequencing data on respiratory samples. This study aimed to provide a high-resolution view on airway microbiome.
Methods: Eighty-one nasopharyngeal (NP) secretions were collected from three groups of pre-school children, including 24 cases hospitalised for HRV-associated AEs, 21 inpatient controls admitted for upper respiratory tract infections (RTI), and 36 community controls without any RTI within four weeks. Extracted genomic DNA was sent for WGS sequencing by Illumina HiSeq X Ten platform. Host contamination was removed using kneadData with default human reference (GRCh37/hg19). Approximately 1.4-4% reads deemed as non-human were used to generate taxonomy profiles through MetaPhlAn2. Alpha-diversity was calculated as Shannon index, and LDA Effect Size (LEfSe) analysis was conducted to identify the most representative microbes for each group. HUMAnN2 was used for predicting metabolic function.
Results: The mean (SD) age of cases, inpatient controls and community controls was 3.5 (1.0), 3.5 (1.0) and 4.9 (0.7) years respectively. Biodiversity in AE group was significant lower than community controls (median [IQR]: 0 [0-0.749] vs 1.073 [0.787-1.941], P=0.0002) but similar to inpatient RTI group (0.692 [0-0.996], P=0.11). LEfSe analysis revealed Dolosigranulum pigrum to be the most characteristic species among community controls (log LDA score 5.57, P=0.0025) while Actinobacteria was significantly more abundant in this group (log LDA score 4.59, P=0.0063). In patients with AE, Proteobacteria was the only significant phylum (log LDA score 5.11, P=0.0441) while no specific species were identified as representative. Two pathways on inosine-5’-phosphate biosynthesis was identified in various bacteria from both control groups but not AE patients.
Conclusions: Pre-school children with AE had lower diversity in their NP microbiome in which Proteobacteria is predominant. Our results suggest that Dolosigranulum pigrum may protect against AE. Further longitudinal studies are needed to investigate the dynamic differences of airway microbiome between stable asthma patients and those with AE.
Funding: Research Committee’s One-off Fund for Research (3132910) of CUHK and Hong Kong Institute of Allergy Research Grant 2018
著者Yu Ping Song, Jamie Sui-Lam Kwok, Haoyi Weng, Man-fung Tang, Christine Tung, Renee Wan-yi Chan, Kin-pong Tao, Gary Wing-kin Wong, Maggie Haitian Wang, Stephen Kwok-wing Tsui, Ting-fan Leung
會議名稱INFECTION 2019 (16th Annual Scientific Meeting)
會議地點Shaw Auditorium, School of Public Health Building, Prince of Wales Hospital, Shatin, Hong Kong

上次更新時間 2019-26-11 於 14:17