Journal Article

DZNE-2024-00352

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Faecal microbial transfer and complex carbohydrates mediate protection against COPD.

Budden, K. F. ; Shukla, S. D. ; Bowerman, K. L. ; Vaughan, A. ; Gellatly, S. L. ; Wood, D. L. A. ; Lachner, N. ; Idrees, S. ; Rehman, S. F. ; Faiz, A. ; Patel, V. K. ; Donovan, C. ; Alemao, C. A. ; Shen, S. ; Amorim, N. ; Majumder, R. ; Vanka, K. S. ; Mason, J. ; Haw, T. J. ; Tillet, B. ; Fricker, M. ; Keely, S. ; Hansbro, N. ; Belz, G. T. ; Horvat, J. ; Ashhurst, T. ; van Vreden, C. ; McGuire, H. ; Fazekas de St Groth, B. ; King, N. J. C. ; Crossett, B. ; Cordwell, S. J. ; Bonaguro, L.DZNE* ; Schultze, J. L.DZNE* ; Hamilton-Williams, E. E. ; Mann, E. ; Forster, S. C. ; Cooper, M. A. ; Segal, L. N. ; Chotirmall, S. H. ; Collins, P. ; Bowman, R. ; Fong, K. M. ; Yang, I. A. ; Wark, P. A. B. ; Dennis, P. G. ; Hugenholtz, P. ; Hansbro, P. M.

2024
BMJ Publishing Group London

This record in other databases:    

Please use a persistent id in citations: doi:10.1136/gutjnl-2023-330521

Abstract: Chronic obstructive pulmonary disease (COPD) is a major cause of global illness and death, most commonly caused by cigarette smoke. The mechanisms of pathogenesis remain poorly understood, limiting the development of effective therapies. The gastrointestinal microbiome has been implicated in chronic lung diseases via the gut-lung axis, but its role is unclear.Using an in vivo mouse model of cigarette smoke (CS)-induced COPD and faecal microbial transfer (FMT), we characterised the faecal microbiota using metagenomics, proteomics and metabolomics. Findings were correlated with airway and systemic inflammation, lung and gut histopathology and lung function. Complex carbohydrates were assessed in mice using a high resistant starch diet, and in 16 patients with COPD using a randomised, double-blind, placebo-controlled pilot study of inulin supplementation.FMT alleviated hallmark features of COPD (inflammation, alveolar destruction, impaired lung function), gastrointestinal pathology and systemic immune changes. Protective effects were additive to smoking cessation, and transfer of CS-associated microbiota after antibiotic-induced microbiome depletion was sufficient to increase lung inflammation while suppressing colonic immunity in the absence of CS exposure. Disease features correlated with the relative abundance of Muribaculaceae, Desulfovibrionaceae and Lachnospiraceae family members. Proteomics and metabolomics identified downregulation of glucose and starch metabolism in CS-associated microbiota, and supplementation of mice or human patients with complex carbohydrates improved disease outcomes.The gut microbiome contributes to COPD pathogenesis and can be targeted therapeutically.

Keyword(s): Humans (MeSH) ; Mice (MeSH) ; Animals (MeSH) ; Pulmonary Disease, Chronic Obstructive: etiology (MeSH) ; Lung: metabolism (MeSH) ; Lung: pathology (MeSH) ; Pneumonia: etiology (MeSH) ; Inflammation: metabolism (MeSH) ; Carbohydrates: pharmacology (MeSH) ; BASIC SCIENCES ; COLONIC MICROFLORA ; DIETARY FIBRE ; IMMUNOLOGY ; INFLAMMATORY DISEASES ; Carbohydrates

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Contributing Institute(s):

1. Clinical Single Cell Omics (CSCO) / Systems Medicine (AG Schultze)
2. Platform for Single Cell Genomics and Epigenomics (Schultze - PRECISE)

Research Program(s):

1. 354 - Disease Prevention and Healthy Aging (POF4-354) (POF4-354)
2. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Experiment(s):

1. Platform for Single Cell Genomics and Epigenomics at DZNE University of Bonn

Appears in the scientific report 2024

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Database coverage:
; ; ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 20 ; JCR ; National-Konsortium ; PubMed Central ; SCOPUS ; Web of Science Core Collection

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