Gut microbiota modulates COPD pathogenesis: role of anti-inflammatory Parabacteroides goldsteinii lipopolysaccharide

• Published in: Gut Vol. 71; no. 2; pp. 309 - 321
• Main Authors: Lai, Hsin-Chih, Lin, Tzu-Lung, Chen, Ting-Wen, Kuo, Yu-Lun, Chang, Chih-Jung, Wu, Tsung-Ru, Shu, Ching-Chung, Tsai, Ying-Huang, Swift, Simon, Lu, Chia-Chen
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd and British Society of Gastroenterology 01.02.2022; BMJ Publishing Group LTD
• Subjects: Animals; Antibiotics; Bacteroidetes - isolation & purification; Chronic obstructive pulmonary disease; Cigarette smoking; Clinical medicine; Digestive system; Discriminant analysis; Disease Models, Animal; Experiments; Fecal Microbiota Transplantation; Flow cytometry; Gastrointestinal Microbiome - physiology; Gastrointestinal tract; Gene expression; Genomes; Gut microbiota; Histopathology; immunology; Inflammation; intestinal microbiology; Intestinal microflora; Laboratory animals; Lavage; Lipopolysaccharides; Lipopolysaccharides - metabolism; Lung diseases; Metabolomics; Mice; Mice, Inbred C57BL; Microbiota; Mitochondria; Mortality; Obstructive lung disease; Oral administration; Parabacteroides; Pathogenesis; Pulmonary Disease, Chronic Obstructive - etiology; Pulmonary Disease, Chronic Obstructive - metabolism; Pulmonary Disease, Chronic Obstructive - pathology; Respiratory tract; Signal transduction; Smoking; TLR4 protein; Toll-like receptors; Transplantation; Tumor necrosis factor-TNF; Variance analysis; United States > US; Taiwan; intestinal microbiology; immunology
• ISSN: 0017-5749; 1468-3288; 1468-3288
• DOI: 10.1136/gutjnl-2020-322599

ObjectiveChronic obstructive pulmonary disease (COPD) is a global disease characterised by chronic obstruction of lung airflow interfering with normal breathing. Although the microbiota of respiratory tract is established to be associated with COPD, the causality of gut microbiota in COPD development is not yet established. We aimed to address the connection between gut microbiota composition and lung COPD development, and characterise bacteria and their derived active components for COPD amelioration.DesignA murine cigarette smoking (CS)-based model of COPD and strategies evaluating causal effects of microbiota were performed. Gut microbiota structure was analysed, followed by isolation of target bacterium. Single cell RNA sequencing, together with sera metabolomics analyses were performed to identify host responsive molecules. Bacteria derived active component was isolated, followed by functional assays.ResultsGut microbiota composition significantly affects CS-induced COPD development, and faecal microbiota transplantation restores COPD pathogenesis. A commensal bacterium Parabacteroides goldsteinii was isolated and shown to ameliorate COPD. Reduction of intestinal inflammation and enhancement of cellular mitochondrial and ribosomal activities in colon, systematic restoration of aberrant host amino acids metabolism in sera, and inhibition of lung inflammations act as the important COPD ameliorative mechanisms. Besides, the lipopolysaccharide derived from P. goldsteinii is anti-inflammatory, and significantly ameliorates COPD by acting as an antagonist of toll-like receptor 4 signalling pathway.ConclusionThe gut microbiota–lung COPD axis was connected. A potentially benefial bacterial strain and its functional component may be developed and used as alternative agents for COPD prevention or treatment.