Berberine ameliorates DSS-induced intestinal mucosal barrier dysfunction through microbiota-dependence and Wnt/β-catenin pathway

Yalan Dong, Heng Fan, Zhe Zhang, Feng Jiang, Mingyue Li, Haifeng Zhou, Weina Guo, Zili Zhang, Zhenyu Kang, Yang Gui, Zhexing Shou, Junyi Li, Rui Zhu, Yu Fu, Alexey Sarapultsev, Huafang Wang, Shanshan Luo, Ge Zhang, Desheng Hu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disorder of the colon, and it has become one of the world-recognized medical problems as it is recurrent and refractory. Berberine (BBR) is an effective drug for UC treatment. However, the underlying mechanism and targets remain obscure. In this study, we systematically investigated the therapeutic effect and its mechanism of BBR in ameliorating DSS-induced mouse colitis. Expectedly, the colon inflammation was significantly relieved by BBR, and microbiota depletion by antibiotic cocktail significantly reversed the therapeutic effect. Further studies showed that BBR can regulate the abundance and component of bacteria, reestablish the broken chemical and epithelial barriers. Meanwhile, BBR administration dramatically decreased ILC1 and Th17 cells, and increased Tregs as well as ILC3 in colonic tissue of DSS-induced mice, and it was able to regulate the expression of various immune factors at the mRNA level. Moreover, a proteomic study revealed that Wnt/β-catenin pathway was remarkably enhanced in colonic tissue of BBR-treated mice, and the therapeutic effect of BBR was disappeared after the intervention of Wnt pathway inhibitor FH535. These results substantially revealed that BBR restores DSS-induced colon inflammation in a microbiota-dependent manner, and BBR performs its protective roles in colon by maintaining the structure and function of the intestinal mucosal barrier, regulating the intestinal mucosal immune homeostasis and it works through the Wnt/β-catenin pathway. Importantly, these findings also provided the proof that BBR serves as a potential gut microbiota modulator and mucosal barrier protector for UC prevention and therapy.

Original languageEnglish
Pages (from-to)1381-1397
Number of pages17
JournalInternational Journal of Biological Sciences
Volume18
Issue number4
DOIs
Publication statusPublished - 16 Jan 2022

Scopus Subject Areas

  • Applied Microbiology and Biotechnology
  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Cell Biology
  • Developmental Biology

User-Defined Keywords

  • Berberine
  • Intestinal mucosal barrier
  • Microbiota
  • Ulcerative colitis
  • Wnt/β-catenin pathway

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