Gut metabolic profile and its clinical correlation in different stages of COPD

<bold>Background:</bold> This study aims to explore the gut metabolic profile of COPD patients in different disease stages and its relationship with clinical features, so as to further understand the mechanism of the lung-gut axis in COPD. <bold>Methods:</bold> A total of 108 longitudinal feces samples from 35 COPD patients and 12 feces samples from healthy controls were subjected to untargeted metabolic profiling. <bold>Results:</bold> A variety of amino acid metabolic pathways were significantly altered in COPD patients, including arginine, phenylalanine, and histidine metabolism. Branched-chain amino acids were significantly decreased in COPD patients. Phenylalanine metabolite ortho-hydroxyphenylacetic acid was significantly increased in patients with peripheral blood eosinophils >100/μL. Using k-means unsupervised clustering, COPD patients of acute exacerbation (AE) could be divided into two groups with significantly different metabolic profiles (Cluster 1 and 2). FEV1/FVC was significantly lower in Cluster 2 (n=14) than in Cluster 1 (n=21) , the proportion of type II respiratory failure and non-invasive ventilation during hospitalization was significantly higher than Cluster 1. Proline, glycine, phenylalanine, valine and lysine were significantly enriched in Cluster 1. Indole lactic acid, a metabolite of tryptophan in gut microbiota, was significantly enriched in Cluster 1 and positively correlated with FEV1. <bold>Conclusion:</bold> A variety of amino acids and microbial metabolites are altered in COPD patients and associated with clinical features, which can provide clues for the mechanism of lung-gut axis and constitute potential targets for the management of COPD.