Integrated Metabolomics and Gut Microbiota Analysis to Elucidate the Underlying Mechanisms of Xuanfei Heji Against Chronic Obstructive Pulmonary Disease
Xuanfei Heji (XFHJ) is a hospital-formulated herbal preparation and has demonstrated significant clinical efficacy in managing chronic obstructive pulmonary disease (COPD). However, its systemic pharmacological mechanisms and the interplay between host metabolism and microbial communities remain to be fully elucidated. The chemical compounds of XFHJ were analyzed using Q Exactive HF-X system. A rat model of COPD was established via intratracheal lipopolysaccharide instillation combined with cigarette smoke exposure. The therapeutic effects of XFHJ were evaluated by monitoring pulmonary function parameters, lung histopathology, and pro-inflammatory cytokine levels (IL-1beta, IL-6, and TNF-alpha). Serum non-targeted metabolomics and fecal 16S rRNA sequencing were employed to identify differential metabolites and microbial signatures. Spearman's rank correlation was performed to integrate multi-omics data. A total of 57 chemical compounds were identified in XFHJ. XFHJ intervention significantly improved pulmonary function and attenuated lung pathological damage. Elevated levels of pro-inflammatory cytokines were markedly downregulated. Metabolomic analysis revealed that XFHJ primarily modulated tryptophan and glycerophospholipid metabolism. Specifically, XFHJ restored indole-3-carbinol levels and upregulated microbiota-derived metabolites, including indole-3-propionic acid, indoleacrylic acid, and N-hydroxytryptamine. 16S sequencing showed that XFHJ restored microbial diversity and enriched beneficial genera such as Roseburia, unclassified_f_Lachnospiraceae, and specific Clostridia lineages, while reducing the abundance of pathogenic Klebsiella. Spearman analysis highlighted significant positive correlations between bioactive indole derivatives and the enriched Clostridia and Roseburia taxa. Collectively, these findings suggest that XFHJ alleviates COPD-related pathological and inflammatory changes in rats, potentially in association with the regulation of gut microbiota and glycerophospholipid- and tryptophan-related metabolic disturbances.