Induced Sputum Microbial Diversity and Function Changes in Patients with Acute Exacerbations of Chronic Obstructive...

The underlying pathogenesis of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is closely related to airway microbiota dysregulation. Currently, there is a lack of systematic elaboration based on deep metagenomic sequencing regarding the species-level and functional characteristics of the microbiota during AECOPD, as well as its correlation with clinical phenotypes of the host. This study aims to systematically analyze the taxonomic composition and functional profile changes of the microbiota in induced sputum samples from COPD patients during the stable and acute exacerbation periods using metagenomic next-generation sequencing and to explore their correlations with clinical indicators through metagenomic methods.

A total of 66 patients with COPD were recruited from the Department of Respiratory and Critical Care Medicine at Jiading District Central Hospital in Shanghai, China. Of these, 49 induced sputum samples were obtained from 47 patients (17 in the stable group; 30 in the acute exacerbation group) after the quality control with DNA extraction and deep metagenomic sequencing. The species annotation and functional analysis were conducted using bioinformatics procedures, and microbial α-diversity analysis, LEfSe analysis was performed to identify differentially expressed markers. Spearman correlation analysis was used to evaluate the correlation between microbial/functional characteristics and a series of clinical indicators.

The α-diversity of the sputum microbiota in AECOPD patients was significantly lower at the species level compared to the stable stage (p < 0.01), and the community structure also underwent significant changes. Functional annotation and comparative analysis further identified 9 KEGG pathways (ko00970, ko04112, ko03420, ko03440, ko03060/ko03070, ko03410, ko04930, and ko00680) and 1 eggNOG functional category (M: Cell wall/membrane/envelope biogenesis) that differed significantly between the two groups. Among them, pathways such as methane metabolism were downregulated in the exacerbation period.

This study revealed significant dysregulation of the airway microbiome in AECOPD patients at species-level diversity, community structure, and functional metabolism, providing a molecular basis for the discovery of functional biomarkers and therapeutic targets in the microbiome.