Abstract

The traditional Chinese medicine (TCM)–Chaihu Shugan Formula (CSF), consisting of several Chinese botanical drugs like Bupleurum, is derived from the ancient Chinese pharmacopeia. It has been used for more than thousands of years in various suboptimal health statuses and diseases induced by chronic stress based on empirical therapy. Recent studies confirm the role of CSF in the development of many diseases, including depression, stress-induced hepatic injury and tumors. However, little has been known about the mechanisms behind the health effects of CSF. Here, we investigate the influence of CSF on the modulation of the simulated colonic microbiota of five healthy donors, gut barrier integrity, and intestinal immunity by combining the simulator of the human intestinal microbial ecosystem (SHIME®) technology platform with co-culture of intestinal and immune cells. This approach revealed that CSF stimulated the production of SCFA (acetate, propionate and butyrate) across donors while significantly lowering the production of branched SCFA (bSCFA). In terms of community composition, CSF stimulated a broad spectrum of health-related Bifidobacterium species, which are potent acetate and lactate producers. At the same time, it lowered the abundance of opportunistic pathogenic Escherichia coli. Later, we explore the effect of colonic fermentation of CSF on the gut barrier and intestinal immunity in the Caco-2/THP1-blue™ cell co-culture model. Based on the study using SHIME technology platform, CSF showed protective effects on inflammation-induced intestinal epithelial barrier disruption in all donors. Also, the treatment of CSF showed pronounced anti-inflammatory properties by strongly inducing anti-inflammatory cytokines IL-6 and IL-10 and reducing pro-inflammatory cytokine TNF-α. These findings demonstrate a significant modulatory effect of CSF on intestinal gut microbiota. CSF-microbial fermentation products improved the gut barrier and controlled intestinal inflammation.

Highlights

  • Traditional Chinese medicine (TCM), an empirical medicine that developed for thousands of years, has established its own medical system differing from modern medicine and has been widely used in many Asian countries, especially in China (Cheung, 2011; Xu et al, 2019)

  • Monitoring the pH during a colonic incubation provides a good indication of the production of short-chain fatty acid (SCFA), lactate and ammonium (NH4+). pH decrease was observed in both the negative control and Chaihu Shugan Formula (CSF) treatment groups upon 48 h incubation (Figure 1A)

  • The effect of traditional Chinese medicine–Chaihu Shugan Formula (CSF), consisting of several Chinese botanical drugs like Bupleurum, on the gut microbiome, gut barrier and intestinal immunity was evaluated using in vitro models–a short-term simulation of the human proximal colon combined with Caco-2/THP1 cell co-culture model

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Summary

Introduction

Traditional Chinese medicine (TCM), an empirical medicine that developed for thousands of years, has established its own medical system differing from modern medicine and has been widely used in many Asian countries, especially in China (Cheung, 2011; Xu et al, 2019). Emerging studies show that it has held great potential for health maintenance, clinical management of various diseases, and new drug discovery (Ma et al, 2013; Sucher, 2013; Xiang et al, 2019; Yang et al, 2020). Studies of the animal model showed that CSF could inhibit the inflammatory response in different organs, such as the liver, intestine, and brain (Yang et al, 2014; Jia et al, 2018; Liang et al, 2018). The digestive tract is the first organ to come after CSF oral administration, the impact of CSF fermentation has been poorly described in general and in the gut microenvironment

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