A Refined View of Airway Microbiome in Chronic Obstructive Pulmonary Disease at Species and Strain-levels

Abstract

Little is known about the species and strain-level diversity of the airway microbiome, and its implication in chronic obstructive pulmonary disease (COPD).Here we report the first comprehensive analysis of the COPD airway microbiome at species and strain-levels. The full-length 16S rRNA gene was sequenced from sputum in 98 stable COPD patients and 27 age-matched healthy controls, using the ‘third-generation’ Pacific Biosciences sequencing platform.Individual species within the same genus exhibited reciprocal relationships with COPD and disease severity. Species dominant in health can be taken over by another species within the same genus in GOLD IV patients. Such turnover was also related to enhanced symptoms and exacerbation frequency. Ralstonia mannitolilytica, an opportunistic pathogen, was significantly increased in COPD frequent exacerbators. There were inflammatory phenotype-specific associations of microbiome at the species-level. One group of four pathogens including Haemophilus influenzae and Moraxella catarrhalis, were specifically associated with sputum mediators for neutrophilic inflammation. Another group of seven species, including Tropheryma whipplei, showed specific associations with mediators for eosinophilic inflammation. Strain-level detection uncovered three non-typeable H. influenzae strains PittEE, PittGG and 86-028NP in the airway microbiome, where PittGG and 86-028NP abundances may inversely predict eosinophilic inflammation. The full-length 16S data augmented the power of functional inference and led to the unique identification of butyrate-producing and nitrate reduction pathways as significantly depleted in COPD.Our analysis uncovered substantial intra-genus heterogeneity in the airway microbiome associated with inflammatory phenotypes and could be of clinical importance, thus enabled a refined view of the airway microbiome in COPD.“Take-home” messageThe species-level analysis using the ‘third-generation’ sequencing enabled a refined view of the airway microbiome and its relationship with clinical outcome and inflammatory phenotype in COPD.

Transition of Ralstonia Mannitolilytica From Commensal to Pathogen During Hospitalization: A Catheter Related Bloodstream Infection (CRBSI) Case Caused by R. Mannitolilytica Colonized in The Respiratory Tract

“…Despite negative identi cation of R. mannitolilytica thereafter, the patient continued to suffer from respiratory failure and eventually died, suggesting this microorganism was a benign colonizer [12]. Such nding is in accordance with a recent comprehensive study on airway microbiomes, where presence of R. mannitolilytica was occasionally found colonizing COPD patients and indicating its potential role to recurrent infections and diseases [4]. For the rst time, we report a catheter related bloodstream infection (CRBSI) case caused by R. mannitolilytica in the respiratory tract of a hospitalization COPD patient.…”

“…As a worldwide public health challenge, chronic obstructive pulmonary disease (COPD) ranks the third leading cause of death and overall prevalence ranges from 8.6-13.6% in China [1][2][3]. COPD patients present altered airway microbiome, with Ralstonia mannitolilytica identi ed in a signi cantly higher rate comparing with healthy population [4]. Despite its commonly overlooked role as a commensal, R. mannitolilytica becomes an emerging global opportunistic human pathogen and a causative agent of various infections and diseases, including bacteremia, meningitis, sepsis, peritonitis, osteomyelitis, hemoperitoneum and urinary tract infection [5][6][7][8][9][10].…”

The Microbiome in Cystic Fibrosis Pulmonary Disease

“…This technology provides only a partial view of genes, preventing taxonomic affiliation down to species level for all reads, and describing ecosystems at best at genus level. Conversely, long-read sequencing (e.g., real-time sequencing, Pacific Biosciences; nanopore sequencing, Oxford Nanopore Technologies) can determine genes' full-length, allowing fine microbiome resolution and use of bioinformatic tools such as Picrust software, designed to predict metagenome functional content from marker genes [36]. What are they doing?…”

Why do some asthma patients respond poorly to glucocorticoid therapy?

“…Similar to asthma in cigarette smokers, it has been proposed that cigarette smoke and oxidative stress in COPD may decrease HDAC2 activity [ 22 ] and increase various kinase pathways such as p38 MAPK [ 68 ]. Of note, the lung inflammation in COPD and smokers with asthma is predominantly neutrophilic [ 69 ], and is the basis of defining an asthma−COPD overlap syndrome (ACOS) sharing steroid-refractory Th17 endotype that predisposes to neutrophilia and neutrophilic asthma is associated to steroid resistance [ 70 , 71 ].…”