Seabuckthorn Wuwei Pulvis attenuates chronic obstructive pulmonary disease in rat through gut microbiota-short chain fatty acids axis

Abstract

Ethnopharmacological relevance: Seabuckthorn Wuwei Pulvis (SWP) is a traditional Mongolian medicine used in China. It is composed of Hippophae rhamnoides (berries, 30 g), Aucklandiae costus Falc. (dry root, 25 g), Vitis vinifera F. Cordifolia (berries, 20 g), Glycyrrhiza uralensis Fisch. (dry root, 15 g), and Gardenia jasminoides J. Ellis (desiccative ripe fruit, 10 g). It is clinically applied in the treatment of chronic cough, shortness of breath and phlegm, and chest distress. Past studies demonstrated that Seabuckthorn Wuwei Pulvis improved lung inflammation and chronic bronchitis in mice. However, the effect of Seabuckthorn Wuwei Pulvis on chronic obstructive pulmonary disease (COPD) in rats and the underlying action mechanism is not fully understood.

Aim of the study: To evaluate the anti-COPD effect of Seabuckthorn Wuwei Pulvis and investigate whether its ameliorative effect is correlated with the composition of gut microbiota and its metabolites.

Materials and methods: The effects of Seabuckthorn Wuwei Pulvis on a COPD rat model were established by exposure to lipopolysaccharide (LPS) and smoking. These effects were then evaluated by monitoring the animal weight, pulmonary function, lung histological alteration, and the levels of inflammatory factors (tumor necrotic factor [TNF]-α, interleukin [IL]-8, IL-6, and IL-17). Furthermore, the serum LPS and fluorescein isothiocyanate-dextran levels were detected by using an enzyme-linked immunosorbent assay and fluorescence microplate reader, respectively. Tight junction proteins (ZO-1 and occludin-1) in the small intestine were detected by performing real-time quantitative polymerase chain reactions and Western blotting to evaluate the intestinal barrier function. The contents of short-chain fatty acids (SCFAs) in the feces of rats were determined by gas chromatography-mass spectrometry. 16S rDNA high throughput sequencing was used to investigate the effect of SWP on the gut microbiota of COPD rats.

Results: Treatment with low and median doses of SWP significantly increased the pulmonary function (forced expiratory volume [FEV] 0.3, forced vital capacity [FVC], and FEV0.3/FVC), decreased the levels of TNF-α, IL-8, IL-6, and IL-17 in the lung, and attenuated the infiltration of inflammatory cells into the lung. The low and median doses of SWP shaped the composition of gut microbiota, which increased the abundances of Ruminococcaceae, Christensenellaceae, and Aerococcaceae, increased the productions of acetic acid, propionic acid, and butyric acid, and upregulated the expression of ZO-1 and occludin-1 in the small intestine of COPD rats.

Conclusion: SWP improved pulmonary functions and inhibited the inflammatory response by shaping the gut microbiota, increasing SCFA production, and strengthening the intestinal barrier function in rats with COPD induced by LPS and smoking.

Keywords: Chronic obstructive pulmonary disease; Gut microbiota; SCFAs; Seabuckthorn Wuwei Pulvis.