Investigation into actions of Xiebai and Zengye decoction on cough sensitivity, airway inflammation and gut microbiota in the rat model of post-infectious cough

Abstract

This work was undertaken to observe therapeutic effect of Xiebai and Zengye (XBZY) decoction on post-infectious cough (PIC) in rats, as well as its effect on gut microbiota and the exploration of the intestinal microecological mechanisms of XBZY decoction in the treatment of PIC. Using a random number table, the rats that were successfully modelled were assigned to the PIC, XBZY group (14.8 g/kg/d), and montelukast sodium treatment (MAS) group (1 mg/kg/d). The cough sensitivity of rats and changes in fecal water content were assessed, and serum interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α) levels were determined by ELISA. The histopathological changes in the bronchus and colon tissues were observed under the microscope after hematoxylin-eosin staining. Short-chain fatty acids (SCFAs) in fecal samples were measured by gas chromatography, and changes in gut microbiota were observed using 16S rRNA sequencing. The PIC rats showed decreased fecal water content, increased cough sensitivity, elevated serum TNF-α and IL-8 levels, and higher bronchitis scores comparing to normal control group. The PIC rats showed reductions in SCFAs and significant changes in the structure of gut microbiota. XBZY decoction intervention led to increased fecal water content in rats, reduced cough sensitivity, decreased serum IL-8 and TNF-α levels, decreased bronchitis scores, and alleviated inflammatory cell infiltration was observed in the colonic mucosa. Additionally, elevated SCFAs levels were observed in the PIC rats. XBZY decoction intervention improved alpha-/beta-diversity, and corrected microbiota imbalance in PIC rats. SCFAs, TNF-α and IL-8, acetic acid was revealed to be positively associated with Allobaculum but inversely correlated with unclassified_f_Oscillospiraceae; propanoic acid was positively associated with Lactobacilli but negatively associated with Romboutsia; butanoic acid exhibited positive correlations with Akkermansia and Lactobacilli, but negative correlations with unclassified_f_Oscillospiraceae, Eubacterium_xylanophilum_group, and Lachnospiraceae_NK4A136_group; Additionally, TNF-α was inversely linked to Allobaculum, while IL-8 was positively related to Romboutsia and Turicibacter. In conclusion, XBZY decoction significantly reduced cough sensitivity and airway inflammation in PIC rats while ameliorating stool dryness and colonic inflammation. The protective effects of XBZY decoction could be linked to modulat gut microbiota in PIC rats, and regulat SCFAs contents in PIC rats, while the regulator mechanisms of XBZY decoction in gut microbiota still requires further in-depth investigation.