RESUMEN
Rationale: Long-term antibiotic use for managing chronic respiratory disease is increasing; however, the role of the airway resistome and its relationship to host microbiomes remains unknown.Objectives: To evaluate airway resistomes and relate them to host and environmental microbiomes using ultradeep metagenomic shotgun sequencing.Methods: Airway specimens from 85 individuals with and without chronic respiratory disease (severe asthma, chronic obstructive pulmonary disease, and bronchiectasis) were subjected to metagenomic sequencing to an average depth exceeding 20 million reads. Respiratory and device-associated microbiomes were evaluated on the basis of taxonomical classification and functional annotation including the Comprehensive Antibiotic Resistance Database to determine airway resistomes. Co-occurrence networks of gene-microbe association were constructed to determine potential microbial sources of the airway resistome. Paired patient-inhaler metagenomes were compared (n = 31) to assess for the presence of airway-environment overlap in microbiomes and/or resistomes.Measurements and Main Results: Airway metagenomes exhibit taxonomic and metabolic diversity and distinct antimicrobial resistance patterns. A "core" airway resistome dominated by macrolide but with high prevalence of ß-lactam, fluoroquinolone, and tetracycline resistance genes exists and is independent of disease status or antibiotic exposure. Streptococcus and Actinomyces are key potential microbial reservoirs of macrolide resistance including the ermX, ermF, and msrD genes. Significant patient-inhaler overlap in airway microbiomes and their resistomes is identified where the latter may be a proxy for airway microbiome assessment in chronic respiratory disease.Conclusions: Metagenomic analysis of the airway reveals a core macrolide resistome harbored by the host microbiome.
Asunto(s)
Asma/microbiología , Bronquiectasia/microbiología , Farmacorresistencia Bacteriana/genética , Disbiosis/microbiología , Macrólidos , Metagenómica , Microbiota/genética , Enfermedad Pulmonar Obstructiva Crónica/microbiología , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos , Estudios de Casos y Controles , Femenino , Fluoroquinolonas , Humanos , Masculino , Persona de Mediana Edad , Nebulizadores y Vaporizadores/microbiología , Índice de Severidad de la Enfermedad , Resistencia a la Tetraciclina/genética , Resistencia betalactámica/genéticaRESUMEN
Asthma imposes a significant burden on the health system and patients' quality of life. Within Asia, there is large variability in several cultural, social and economic factors ultimately influencing the management of asthma. Differences in risk factors and asthma management practices across Asia make asthma a truly 'mixed-bag' phenomenon. With the advent of biological agents and the consequent emphasis on asthma phenotyping and endotyping, it is more important than ever to understand the diverse nature of asthma as a disease. This is a collaborative review within Asia to highlight the differences in management of adult asthma, and the local modifications that are made to international guidelines. This review paves the way for a future Asian collaborative network in asthma epidemiological research.