Integrative analysis of the efficacy and mechanism on Changkang granules for treating irritable bowel syndrome rats

Background: Irritable Bowel Syndrome (IBS) is a chronic disease with recurrent functional gastrointestinal. The pathogenesis and pathophysiology of this disease are highly complex, and the existing pharmaceutical treatment methods do not address all IBS symptoms. It is very important to develop a drug that can treat the disease and clarify its mechanism of action. This study aimed to address the effects of Changkang granules on IBS rats and then exploring the possible underlying mechanism using the gut microbiota -metabolomics method. Methods: The IBS rats was established by administering senna leaf water and applying restraint stress to investigate the efficacy of Changkang granules. With the methods of 16S rRNA sequencing technology and non-targeted metabolomics to explore the role of Changkang granules in IBS and identify the potential mechanisms involved. Results: Changkang granules can improve the visceral hypersensitivity of IBS by inhibiting the serum SP level of model rats, increasing the expression of serum CGRP and VIP in colon tissue. The underlying mechanism of action could involve increase the beneficial bacteria such as Bifidobacteria, Clostridium and Coprococcus, thereby up-regulating the levels of metabolites such as arachidonic acid (DHA) and γ-aminobutyric acid (GABA), down-regulating the expression of 2-hydroxybutyric acid (HA), inhibiting intestinal microecological disorders, improving the protective effect on the intestine, interfering with the MAPK metabolic pathway by reducing HA content, reducing inflammatory factors such as NF-κB, preventing inflammation, improving disease resistance, and relieving IBS symptoms. Conclusion: Changkang granule has a therapeutic effect on IBS rats, and its mechanism may be achieved by regulating gut microbiota and regulating metabolites such as GABA and 2-hydroxybutyric acid HA, which highlights a novel method for the treatment of IBS.