Chang-Kang-Fang Ameliorates Experimental Diarrhea Predominant Irritable Bowel Syndrome by Regulating Gut Microbiota and Gut -Brain Axis

Abstract Background: Chang-Kang-Fang formula (CKF), a multi-herb traditional Chinese medicinal formula, has been clinically used for treatment of irritable bowel syndrome with diarrhea (IBS-D). Though we have reported the compounds of CKF and the therapeutic effect on IBS-D rats, the exact mechanism underlying is still not clear. The aim of this study is to clearly define the effect of CKF on IBS-D by regulating gut microbiota and gut-brain axis. Method: We investigated the effects of CKF on IBS-D rat model, established by psychosocial stress (restraint) combined with the peripheral stimulation (senna leaf gavage) stress. The changed of body weight and the number of fecal pellets was investigated during the experiment. The effect on intestinal sensitivity was assessed based on the abdominal withdrawal reflex (AWR) scores and the intestinal permeability, the expression of ZO-1, measured by immunohistochemistry. The effect of CKF on gut-brain axis was evaluated by the expression of 5-HT through immunohistochemistry. The composition of gut microbiota was detected through 16sRNA. Results: Administration of CKF significantly have shown the therapeutic effect on IBS-D rats, involving decreased the score of AWR and increased the number of pellets, though there were no different on body weight change. In addition, CKF could upregulated the expression of ZO-1 in colon and downregulated the expression of 5-HT in colon and brain Moreover, CKF could rebalance the gut microbiota of IBS-D, increasing the abundance of Lactobacillu, Allobaculum, Roseburia and Lachnospiraceae_NK4A136. Conclusion: CKF potentially alleviates IBS-D through regulating gut microbiota and gut-brain axis.