Berberine Regulates Treg/Th17 Balance to Treat Ulcerative Colitis Through Modulating the Gut Microbiota in the Colon.

Huantian Cui,Pengwei Zhuang,Xiaoyu Zhang,Jin Lin,Xiaoqian Chu,Li Wang,Yuhong Bian,Beitian Jia,Shuwu Zhao,Junchen Li,Yuzi Cai

doi:10.3389/fphar.2018.00571

Huantian Cui, Pengwei Zhuang + Show 9 more

Open Access

https://doi.org/10.3389/fphar.2018.00571

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Abstract

Berberine (BBR), an alkaloid isolated from Rhizoma Coptidis, Cortex Phellode, and Berberis, has been widely used in the treatment of ulcerative colitis (UC). However, the mechanism of BBR on UC is unknown. In this study, we investigated the activities of T regulatory cell (Treg) and T helper 17 cell (Th17) in a dextran sulfate sodium (DSS)-induced UC mouse model after BBR administration. We also investigated the changes of gut microbiota composition using 16S rRNA analysis. We also examined whether BBR could regulate the Treg/Th17 balance by modifying gut microbiota. The mechanism was further confirmed by depleting gut microbiota through a combination of antibiotic treatment and fecal transplantations. Results showed that BBR treatment could improve the Treg/Th17 balance in the DSS-induced UC model. BBR also reduced diversity of the gut microbiota and interfered with the relative abundance of Desulfovibrio, Eubacterium, and Bacteroides. Moreover, BBR treatment did not influence the Treg/Th17 balance after the depletion of gut microbiota. Our results also revealed that fecal transplantation from BBR-treated mice could relieve UC and regulate the Treg/Th17 balance. In conclusion, our study provides evidence that BBR prevents UC by modifying gut microbiota and regulating the balance of Treg/Th17.

Highlights

Ulcerative colitis (UC) is a chronic and nonspecific inflammatory disease that has a prolonged disease duration and is difficult to cure
We further investigated the effect of BBR on T regulatory cells (Treg)/T helper cell 17 (Th17) balance, one of the important mechanisms in ulcerative colitis (UC) progression
Th17 cells differentiate from naïve CD4+T cells through stimulation by transforming growth factor (TGF)-β and IL-6

Summary

Introduction

Ulcerative colitis (UC) is a chronic and nonspecific inflammatory disease that has a prolonged disease duration and is difficult to cure. Hereditary factors, the gut environment, immune response, cell apoptosis, and infection have been implicated in UC. During UC progression, the T helper cell 17 (Th17) population, which contributes to inflammation, is usually increased, while T regulatory cells (Treg), which inhibit Th17 activity, are decreased (Luo et al, 2017). UC patients exhibit gut microbiota dysfunction which results in increased permeability of the intestinal epithelial cell barrier, triggering inflammatory response of the intestine (Hoque et al, 2000). Probiotics, which could regulate the immune function and promote intestinal mucosa repair, are decreased in UC patients (Shen et al, 2014). Modulating gut microbiota to promote intestinal mucosa repair is of clinical importance in UC studies (Cui et al, 2004; Zhao H.M. et al, 2013)

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