The Alleviation Effect Of Three Kinds Of Traditional Chinese Medicine Compound And Their Fermented Decoction On Dysbacteriotic Diarrhea Mice Induced By Antibiotic

[Objective] This study was aimed to investigate the mitigative effect of Traditional Chinese Medicine(TCM)and fermented TCM(FTCM)with Lactobacillus plantarum(LP)in antibiotic-associated diarrhea(AAD),and identify the compounds of Sijunzi(S)and Fermented S(FS).[Methods] The dysbacteriotic diarrhea mice induced by ceftriaxone sodium(CS)were treated with LP,Buzhongyiqi(B),Sijunzi(S),Shenlingbaizhu(SH),Fermented B(FB),FS,and Fermented SH(FSH).The diarrhea indexes,the abundance of some gut bacteria,intestinal morphometrics,and the m RNA expressions related to intestinal barrier function were assessed at multilevels.In addition,S and FS were chosen to identify and relatively quantify the compounds by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF/MS),and different expressed compounds were analysed.[Results] 1.The results of diarrhea evaluation showed that compared to the control group,the CS group significantly increased the fecal output weight,the total number of fecal output,fecal water content,the loose stool rate and diarrhea rate(P < 0.05),indicating that the diarrhea model was successfully established.Compared to the CS group,the TCM group,the LP group and the FTCM group all showed different degrees of relieving effects,and the FTCM showed more sustained effects.2.The fecal bacterial culture test showed that the intestinal flora of diarrhea mice was destroyed.Compared to the control group,the numbers of lactobacillus,bifidobacterium,enterococcus and colibacillus in the ceftriaxone sodium group were significantly decreased(P < 0.05).Compared to the CS group,the numbers of the above four types of bacteria were significantly increased(P < 0.05)in different degrees in other treatment groups,and some treatment groups returned to the control group level.3.The intestinal morphology and intestinal barrier function of mice in the CS group were impaired.It was observed that CS caused intestinal mucosal injury in duodenum,jejunum and ileum,including short and broad villi,deep crypts,incomplete and fractured structures.And the aquaporin(AQP)and tight junction protein(TJ)m RNA expression level was significantly reduced(P < 0.05).Compared to the CS group,the above indices were alleviated in other treatments mice.The intestinal villi of the mice in the treatment group were arranged more neatly and tightly,the structure is relatively complete,and the fermentation group has longer villi and better effects.At the same time,the m RNA expression of AQP and TJ related genes increased significantly(P < 0.05).4.Through UHPLC-Q-TOF/MS identification and relative quantification,it was found that the content of 30 compounds in FS was significantly increased(P < 0.05)compared to S,of which 4compounds were worthy of attention.They may be potential indicators for inhibiting harmful bacteria and improving intestinal development.[Conclusion] All these findings imply that the intestinal side effects caused by CS can be alleviated by Yi-Qi TCM,LP,and FTCM through regulating the intestinal flora and barrier function,which provides an idea of further development and application of them in the clinical use of antibiotics.