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

作者：Hsin‐Chih Lai, Tzu-Lung Lin, Ting-Wen Chen, Yu-Lun Kuo, Chih‐Jung Chang, Tsung-Ru Wu, Ching-Chung Shu, Ying-Huang Tsai, Simon Swift, Chia-Chen Lu · 发表于：Gut · 年份：2021 · DOI：10.1136/gutjnl-2020-322599 · 被引用次数：343 · 研究领域：Gut microbiota and health、Chronic Obstructive Pulmonary Disease (COPD) Research、Delphi Technique in Research

Objective Chronic 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. Design A 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. Results Gut 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. goldsteini...