A novel strategy based on serum metabolite-mediated interactions between the lung and gut microbiota to investigate the protective effect of Flos Farfarae against chronic bronchitis.

Abstract

Chronic bronchitis (CB) is a complex respiratory disease characterized by a persistent cough, dyspnea, and excessive sputum production. Flos Farfarae (FF), derived from the dried flower buds of Tussilago farfara L. (Asteraceae), has a long history of use in Traditional Chinese Medicine (TCM) for treating respiratory ailments. In our study, FF treatment significantly reduced serum interleukin 1β (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) in the CB rats, and hematoxylin and eosin (HE) staining of lung and colon tissues also indicated obvious reduction in inflammatory infiltrates. Additionally, we found that FF treatment markedly decreased the abundance of the lung bacterium Pseudomonas and the gut bacterium Roseburia. Bugbase analysis showed that FF was able to reduce the increased potentially pathogenic bacteria in the lung and gut microbiota of CB rats. Serum pseudo-targeted metabolomic analysis showed that FF significantly modulated 31 differential serum metabolites, including palmitoleic acid and indoxyl sulfate. Furthermore, correlation-based ensemble network analysis revealed that interactions between lung and gut microbiota were significantly increased in the CB rats. Similarly, interactions between lung microbiota and serum metabolites, as well as between gut microbiota and serum metabolites, were significantly enhanced. However, FF treatment significantly reduced these interactions. FF treatment not only alleviates the inflammatory state of rats with chronic bronchitis by modulating specific lung and gut microbiota and serum metabolites, but also may restore gut and lung microbial homeostasis by decreasing serum metabolite-mediated interactions between the lung and gut microbiota, thereby resulting in therapeutic effects in rats with CB. We systematically evaluated the efficacy of the traditional Chinese medicine FF in CB from the innovative perspective of serum metabolite-mediated interactions between lung and gut microbiota for the first time.