Comparative metagenomics sequencing analysis of respiratory microbiome in healthy and infected individuals

Abstract

The human respiratory microbiome plays an essential role in respiratory health and disease. Next-generation sequencing (NGS) technologies have given us an unprecedented opportunity for studying the microbiome of complex infectious diseases. This thesis contains two comparative metagenomes studies of the human respiratory microbiome based on NGS data analysis, with the objective to understand the underlying microbiome profiles of patients with respiratory infections.

The first one is a metagenomics study of individuals before and during seasonal influenza infection. Nasal swabs were collected from ten healthy subjects at baseline and subjected to whole-genome shotgun sequencing. During the second visit, five subjects remained healthy and five were infected. The microbiome of subjects who remained healthy at the second time point was compared with those who got infected. We observed that the predominated bacteria in the nasal bacterial communities were Actinobacteria, Bacteroidetes, Firmicutes and Proteobacteria. The abundance change of Actinobacteria in infected subjects was significantly different from that of healthy subjects, which is mainly due to the change of Corynebacterium at genus rank. The bacterial communities of infected subjects appeared to be more diverse than healthy subjects. For functional analysis, the proportion at baseline for various categories did not differ from that at the second time point for both the healthy and infected groups.

The second study is a longitudinal metagenomics investigation of healthy and diseased individuals with respiratory tract infections. Two metagenomics datasets, the longitudinal seasonal influenza shotgun sequencing data and a 16s rRNA gene sequencing dataset from rhinovirus-infected nasal lavage fluid samples, were used for the longitudinal investigation. The mixed-effect ZIBR model was applied to identify taxa associated with respiratory infections. For the first dataset, we did not observe any significant difference in the relative abundance of the dominant phyla between healthy control and influenza-infected group. However, for the second, we found that Corynebacterium (genus member of Actinobacteria) had significant differences between the healthy and infected groups.

In conclusion, our study suggests that the microbial community diversity changes when subjects get infected with seasonal influenza, and Corynebacterium might be closely associated with the development of respiratory infections.