TY  - JOUR
AU  - Budden, Kurtis F
AU  - Shukla, Shakti D
AU  - Bowerman, Kate L
AU  - Vaughan, Annalicia
AU  - Gellatly, Shaan L
AU  - Wood, David L A
AU  - Lachner, Nancy
AU  - Idrees, Sobia
AU  - Rehman, Saima Firdous
AU  - Faiz, Alen
AU  - Patel, Vyoma K
AU  - Donovan, Chantal
AU  - Alemao, Charlotte A
AU  - Shen, Sj
AU  - Amorim, Nadia
AU  - Majumder, Rajib
AU  - Vanka, Kanth S
AU  - Mason, Jazz
AU  - Haw, Tatt Jhong
AU  - Tillet, Bree
AU  - Fricker, Michael
AU  - Keely, Simon
AU  - Hansbro, Nicole
AU  - Belz, Gabrielle T
AU  - Horvat, Jay
AU  - Ashhurst, Thomas
AU  - van Vreden, Caryn
AU  - McGuire, Helen
AU  - Fazekas de St Groth, Barbara
AU  - King, Nicholas J C
AU  - Crossett, Ben
AU  - Cordwell, Stuart J
AU  - Bonaguro, Lorenzo
AU  - Schultze, Joachim L
AU  - Hamilton-Williams, Emma E
AU  - Mann, Elizabeth
AU  - Forster, Samuel C
AU  - Cooper, Matthew A
AU  - Segal, Leopoldo N
AU  - Chotirmall, Sanjay H
AU  - Collins, Peter
AU  - Bowman, Rayleen
AU  - Fong, Kwun M
AU  - Yang, Ian A
AU  - Wark, Peter A B
AU  - Dennis, Paul G
AU  - Hugenholtz, Philip
AU  - Hansbro, Philip M
TI  - Faecal microbial transfer and complex carbohydrates mediate protection against COPD.
JO  - Gut
VL  - 73
IS  - 5
SN  - 0017-5749
CY  - London
PB  - BMJ Publishing Group
M1  - DZNE-2024-00352
SP  - 751 - 769
PY  - 2024
AB  - 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.
KW  - Humans
KW  - Mice
KW  - Animals
KW  - Pulmonary Disease, Chronic Obstructive: etiology
KW  - Lung: metabolism
KW  - Lung: pathology
KW  - Pneumonia: etiology
KW  - Inflammation: metabolism
KW  - Carbohydrates: pharmacology
KW  - BASIC SCIENCES (Other)
KW  - COLONIC MICROFLORA (Other)
KW  - DIETARY FIBRE (Other)
KW  - IMMUNOLOGY (Other)
KW  - INFLAMMATORY DISEASES (Other)
KW  - Carbohydrates (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:38331563
DO  - DOI:10.1136/gutjnl-2023-330521
UR  - https://pub.dzne.de/record/268848
ER  -