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Faecal microbial transfer and complex carbohydrates mediate protection against COPD.

Gut

Authors: Kurtis F Budden, Shakti D Shukla, Kate L Bowerman, Annalicia Vaughan, Shaan L Gellatly, David L A Wood, Nancy Lachner, Sobia Idrees, Saima Firdous Rehman, Alen Faiz, Vyoma K Patel, Chantal Donovan, Charlotte A Alemao, Sj Shen, Nadia Amorim, Rajib Majumder, Kanth S Vanka, Jazz Mason, Tatt Jhong Haw, Bree Tillet, Michael Fricker, Simon Keely, Nicole Hansbro, Gabrielle T Belz, Jay Horvat, Thomas Ashhurst, Caryn van Vreden, Helen McGuire, Barbara Fazekas de St Groth, Nicholas J C King, Ben Crossett, Stuart J Cordwell, Lorenzo Bonaguro, Joachim L Schultze, Emma E Hamilton-Williams, Elizabeth Mann, Samuel C Forster, Matthew A Cooper, Leopoldo N Segal, Sanjay H Chotirmall, Peter Collins, Rayleen Bowman, Kwun M Fong, Ian A Yang, Peter A B Wark, Paul G Dennis, Philip Hugenholtz, Philip M Hansbro

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 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 and 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.

© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.

PMID: 38331563

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