Faecal microbial transfer and complex carbohydrates mediate protection against COPD

• Published in: Gut Vol. 73; no. 5; pp. 751 - 769
• Main Authors: Budden, Kurtis F, Shukla, Shakti D, Bowerman, Kate L, Vaughan, Annalicia, Gellatly, Shaan L, Wood, David L A, Lachner, Nancy, Idrees, Sobia, Rehman, Saima Firdous, Faiz, Alen, Patel, Vyoma K, Donovan, Chantal, Alemao, Charlotte A, Shen, Sj, Amorim, Nadia, Majumder, Rajib, Vanka, Kanth S, Mason, Jazz, Haw, Tatt Jhong, Tillet, Bree, Fricker, Michael, Keely, Simon, Hansbro, Nicole, Belz, Gabrielle T, Horvat, Jay, Ashhurst, Thomas, van Vreden, Caryn, McGuire, Helen, Fazekas de St Groth, Barbara, King, Nicholas J C, Crossett, Ben, Cordwell, Stuart J, Bonaguro, Lorenzo, Schultze, Joachim L, Hamilton‐Williams, Emma E, Mann, Elizabeth, Forster, Samuel C, Cooper, Matthew A, Segal, Leopoldo N, Chotirmall, Sanjay H, Collins, Peter, Bowman, Rayleen, Fong, Kwun M, Yang, Ian A, Wark, Peter A B, Dennis, Paul G, Hugenholtz, Philip, Hansbro, Philip M
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd and British Society of Gastroenterology 08.02.2024; BMJ Publishing Group LTD
• Subjects: Alveoli; Animals; Antibiotics; BASIC SCIENCES; Body mass index; Carbohydrates; Carbohydrates - pharmacology; Cell cycle; Chronic obstructive pulmonary disease; Cigarette smoke; Cigarette smoking; COLONIC MICROFLORA; DIETARY FIBRE; Digestive system; Digestive tract; Discriminant analysis; Drug addiction; Flow cytometry; Glucose metabolism; Gut microbiota; Histopathology; Humans; IMMUNOLOGY; Inflammation; Inflammation - metabolism; INFLAMMATORY DISEASES; Intestinal microflora; Lung - metabolism; Lung - pathology; Lung diseases; Metabolism; Metabolomics; Metagenomics; Mice; Microbiomes; Microbiota; Obstructive lung disease; Pathogenesis; Pneumonia - etiology; Proteomics; Pulmonary Disease, Chronic Obstructive - etiology; Respiratory function; Smoking cessation; Tumor necrosis factor-TNF; Veganism; Australia; United States > US; DIETARY FIBRE; IMMUNOLOGY; COLONIC MICROFLORA; INFLAMMATORY DISEASES; BASIC SCIENCES
• ISSN: 0017-5749; 1468-3288; 1468-3288
• DOI: 10.1136/gutjnl-2023-330521

ObjectiveChronic 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.DesignUsing 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.ResultsFMT 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.ConclusionThe gut microbiome contributes to COPD pathogenesis and can be targeted therapeutically.