Dataset Information

Airway Dysbiosis Accelerates Lung Function Decline in Chronic Obstructive Pulmonary Disease (Human UPLC-MS/MS assays)

ABSTRACT:

Progressive decline in lung function is a hallmark of chronic obstructive pulmonary disease (COPD). Although airway dysbiosis occurs in COPD, whether it contributes to disease progression remains unknown. Here, through a longitudinal analysis on 181 COPD individuals from two large cohorts involving four UK clinical centers, we showed that baseline airway dysbiosis, characterized by enrichment of opportunistic pathogenic taxa, was associated with rapid forced expiratory volume in one second (FEV1) decline over two years. Co-presence of Moraxella, Staphylococcus and Stenotrophomonas was associated with an accelerated FEV1 decline by 139.7 mL/year. The dysbiosis was associated with exacerbation-related FEV1 fall and sudden FEV1 fall at clinical stability, two critical events contributing to long-term FEV1 decline. The microbiota association with FEV1 decline was validated in a third, independent cohort in China. Human multi-omics, murine and cellular mechanistic studies showed that chronic airway colonization of Staphylococcus aureus promoted lung function decline through producing homocysteine, which elicited an apoptosis-to-NETosis shift in neutrophils toward persistent inflammation via AKT1-S100A8/A9 axis. Prophylactic and therapeutic depletion of S. aureus via bacteriophage restored lung function in emphysema mice. These results provide a fresh approach to slow COPD progression by targeting the airway microbiome.

Linked studies:

UPLC-MS/MS assays of human samples are reported in this study.

UPLC-MS/MS assays of murine samples are reported in MTBLS6894.

UPLC-MS/MS assays of original cohort human samples are reported in MTBLS4017.

INSTRUMENT(S): Liquid Chromatography MS - positive - hilic, Liquid Chromatography MS - negative - hilic

SUBMITTER: Zhang Wang

PROVIDER: MTBLS5423 | MetaboLights | 2023-06-12

REPOSITORIES: MetaboLights

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Dataset's files

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			Action	DRS
	MTBLS5423	Other
	FILES	Other
	a_MTBLS5423_LC-MS_negative_hilic_metabolite_profiling.txt	Txt
	a_MTBLS5423_LC-MS_positive_hilic_metabolite_profiling.txt	Txt
	files-all.json	Other

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Publications

Airway dysbiosis accelerates lung function decline in chronic obstructive pulmonary disease.

Liang Weijie W Yang Yuqiong Y Gong Shenhai S Wei Mingyuan M Ma Yingfei Y Feng Ruipei R Gao Jingyuan J Liu Xiaomin X Tu Fuyi F Ma Wei W Yi Xinzhu X Liang Zhenyu Z Wang Fengyan F Wang Lingwei L Chen Dandan D Shu Wensheng W Miller Bruce E BE Tal-Singer Ruth R Donaldson Gavin C GC Wedzicha Jadwiga A JA Singh Dave D Wilkinson Tom M A TMA Brightling Christopher E CE Chen Rongchang R Zhong Nanshan N Wang Zhang Z

Cell host & microbe 20230518 6

Progressive lung function decline is a hallmark of chronic obstructive pulmonary disease (COPD). Airway dysbiosis occurs in COPD, but whether it contributes to disease progression remains unknown. Here, we show, through a longitudinal analysis of two cohorts involving four UK centers, that baseline airway dysbiosis in COPD patients, characterized by the enrichment of opportunistic pathogenic taxa, associates with a rapid forced expiratory volume in 1 s (FEV1) decline over 2 years. Dys ...[more]

PMID: 37207649

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