Faecal microbial transfer and complex carbohydrates mediate protection against COPD.

Budden, KF; Shukla, SD; Bowerman, KL; Vaughan, A; Gellatly, SL; Wood, DLA; Lachner, N; Idrees, S; Rehman, SF; Faiz, A; Patel, VK; Donovan, C; Alemao, CA; Shen, S; Amorim, N; Majumder, R; Vanka, KS; Mason, J; Haw, TJ; Tillet, B; Fricker, M; Keely, S; Hansbro, N; Belz, GT; Horvat, J; Ashhurst, T; van Vreden, C; McGuire, H; Fazekas de St Groth, B; King, NJC; Crossett, B; Cordwell, SJ; Bonaguro, L; Schultze, JL; Hamilton-Williams, EE; Mann, E; Forster, SC; Cooper, MA; Segal, LN; Chotirmall, SH; Collins, P; Bowman, R; Fong, KM; Yang, IA; Wark, PAB; Dennis, PG; Hugenholtz, P; Hansbro, PM

Faecal microbial transfer and complex carbohydrates mediate protection against COPD.

Budden, KF Shukla, SD Bowerman, KL Vaughan, A

Gellatly, SL Wood, DLA Lachner, N Idrees, S

Rehman, SF Faiz, A

Patel, VK Donovan, C

Alemao, CA Shen, S

Amorim, N Majumder, R

Vanka, KS Mason, J Haw, TJ Tillet, B Fricker, M Keely, S Hansbro, N

Belz, GT Horvat, J Ashhurst, T van Vreden, C McGuire, H Fazekas de St Groth, B King, NJC Crossett, B Cordwell, SJ Bonaguro, L Schultze, JL Hamilton-Williams, EE Mann, E Forster, SC Cooper, MA Segal, LN Chotirmall, SH Collins, P Bowman, R Fong, KM Yang, IA Wark, PAB Dennis, PG Hugenholtz, P Hansbro, PM

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Publisher:: BMJ PUBLISHING GROUP
Publication Type:: Journal Article
Citation:: Gut, 2024, 73, (5), pp. 751-769
Issue Date:: 2024-04-05

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Field	Value	Language
dc.contributor.author	Budden, KF
dc.contributor.author	Shukla, SD
dc.contributor.author	Bowerman, KL
dc.contributor.author	Vaughan, A https://orcid.org/0000-0001-5890-7877
dc.contributor.author	Gellatly, SL
dc.contributor.author	Wood, DLA
dc.contributor.author	Lachner, N
dc.contributor.author	Idrees, S https://orcid.org/0000-0001-8512-7593
dc.contributor.author	Rehman, SF
dc.contributor.author	Faiz, A https://orcid.org/0000-0003-1740-3538
dc.contributor.author	Patel, VK
dc.contributor.author	Donovan, C https://orcid.org/0000-0003-4558-329X
dc.contributor.author	Alemao, CA
dc.contributor.author	Shen, S https://orcid.org/0000-0002-1004-1936
dc.contributor.author	Amorim, N
dc.contributor.author	Majumder, R https://orcid.org/0000-0002-7244-6058
dc.contributor.author	Vanka, KS
dc.contributor.author	Mason, J
dc.contributor.author	Haw, TJ
dc.contributor.author	Tillet, B
dc.contributor.author	Fricker, M
dc.contributor.author	Keely, S
dc.contributor.author	Hansbro, N https://orcid.org/0000-0002-2371-7990
dc.contributor.author	Belz, GT
dc.contributor.author	Horvat, J
dc.contributor.author	Ashhurst, T
dc.contributor.author	van Vreden, C
dc.contributor.author	McGuire, H
dc.contributor.author	Fazekas de St Groth, B
dc.contributor.author	King, NJC
dc.contributor.author	Crossett, B
dc.contributor.author	Cordwell, SJ
dc.contributor.author	Bonaguro, L
dc.contributor.author	Schultze, JL
dc.contributor.author	Hamilton-Williams, EE
dc.contributor.author	Mann, E
dc.contributor.author	Forster, SC
dc.contributor.author	Cooper, MA
dc.contributor.author	Segal, LN
dc.contributor.author	Chotirmall, SH
dc.contributor.author	Collins, P
dc.contributor.author	Bowman, R
dc.contributor.author	Fong, KM
dc.contributor.author	Yang, IA
dc.contributor.author	Wark, PAB
dc.contributor.author	Dennis, PG
dc.contributor.author	Hugenholtz, P
dc.contributor.author	Hansbro, PM
dc.date.accessioned	2024-09-15T03:51:00Z
dc.date.available	2024-01-08
dc.date.available	2024-09-15T03:51:00Z
dc.date.issued	2024-04-05
dc.identifier.citation	Gut, 2024, 73, (5), pp. 751-769
dc.identifier.issn	0017-5749
dc.identifier.issn	1468-3288
dc.identifier.uri	http://hdl.handle.net/10453/180823
dc.description	Free online access at the publisher's site: https://doi.org/10.1136/gutjnl-2023-330521
dc.description.abstract	OBJECTIVE: 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. DESIGN: 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. RESULTS: 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. CONCLUSION: The gut microbiome contributes to COPD pathogenesis and can be targeted therapeutically.
dc.format	Electronic
dc.language	eng
dc.publisher	BMJ PUBLISHING GROUP
dc.relation	http://purl.org/au-research/grants/nhmrc/GNT1079187
dc.relation	http://purl.org/au-research/grants/nhmrc/1175134
dc.relation	Free online access at publisher's site at: https://doi.org/10.1136/gutjnl-2023-330521
dc.relation.ispartof	Gut
dc.relation.isbasedon	10.1136/gutjnl-2023-330521
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	1103 Clinical Sciences, 1114 Paediatrics and Reproductive Medicine
dc.subject.classification	Gastroenterology & Hepatology
dc.subject.classification	3202 Clinical sciences
dc.subject.classification	3210 Nutrition and dietetics
dc.subject.mesh	Humans
dc.subject.mesh	Mice
dc.subject.mesh	Animals
dc.subject.mesh	Pulmonary Disease, Chronic Obstructive
dc.subject.mesh	Lung
dc.subject.mesh	Pneumonia
dc.subject.mesh	Inflammation
dc.subject.mesh	Carbohydrates
dc.subject.mesh	Lung
dc.subject.mesh	Animals
dc.subject.mesh	Humans
dc.subject.mesh	Mice
dc.subject.mesh	Pulmonary Disease, Chronic Obstructive
dc.subject.mesh	Pneumonia
dc.subject.mesh	Inflammation
dc.subject.mesh	Carbohydrates
dc.subject.mesh	Humans
dc.subject.mesh	Mice
dc.subject.mesh	Animals
dc.subject.mesh	Pulmonary Disease, Chronic Obstructive
dc.subject.mesh	Lung
dc.subject.mesh	Pneumonia
dc.subject.mesh	Inflammation
dc.subject.mesh	Carbohydrates
dc.title	Faecal microbial transfer and complex carbohydrates mediate protection against COPD.
dc.type	Journal Article
utslib.citation.volume	73
utslib.location.activity	England
utslib.for	1103 Clinical Sciences
utslib.for	1114 Paediatrics and Reproductive Medicine
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Health
pubs.organisational-group	University of Technology Sydney/Faculty of Science
pubs.organisational-group	University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	University of Technology Sydney/Strength - CFI - Centre for Inflammation
pubs.organisational-group	University of Technology Sydney/All Manual Groups
pubs.organisational-group	University of Technology Sydney/All Manual Groups/Australian Institute for Microbiology & Infection (AIMI)
pubs.organisational-group	University of Technology Sydney/All Manual Groups/Centre for Inflammation (CFI)
pubs.organisational-group	University of Technology Sydney/All Manual Groups/Australian Institute for Microbiology & Infection (AIMI)/Associate Member
utslib.copyright.status	open_access	*
dc.date.updated	2024-09-15T03:50:56Z
dc.rights.holder	© Author(s) (or their employer(s)) 2024. No commercial re-use.
pubs.issue	5
pubs.publication-status	Published online
pubs.volume	73
utslib.citation.issue	5

Abstract:

OBJECTIVE: 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. DESIGN: 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. RESULTS: 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. CONCLUSION: The gut microbiome contributes to COPD pathogenesis and can be targeted therapeutically.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/180823