Abstract

Background: Dietary intervention is an exciting topic in current research of inflammatory bowel disease (IBD). The effect of teasaponin (TS) on IBD has not been fully elucidated. Here, we aim to investigate the intestinal anti-inflammatory activity of TS in a dextran sodium sulfate (DSS)-induced colitis mouse model and identify potential mechanisms.Methods: We applied TS to mice with DSS-induced colitis and then monitored the body weight, disease activity index (DAI) daily. When sacrificed, the intestinal permeability was measured. The analysis of mucin and tight junction proteins was conducted. We detected the inflammatory cytokines, the immune cells and related inflammatory signaling pathways. In addition, the gut microbiota were analyzed by 16S rRNA sequencing and we also performed fecal microbiota transplantation (FMT).Results: It showed that TS ameliorated the colonic damage by lowering the DAI, prolonging the colon length, reducing inflammatory cytokines and improving the mucus barrier. Parallel to down-regulation of the inflammatory cytokines, the fecal lipocalin 2, p-P65, p-STAT3, and neutrophil accumulation were also decreased in TS-treated mice. Microbiota characterization showed that Campylobacteria, Proteobacteria, Helicobacter, and Enterobacteriaceae were the key bacteria associated with IBD. In addition, TS could reverse the Firmicutes/Bacteroidetes (F/B) ratio and increase the beneficial bacteria, including Akkermansia and Bacteroides. TS ameliorated DSS-induced colitis by regulating the gut microbiota, and the gut microbiota could regulate gut inflammation.Conclusions: These studies demonstrated that TS ameliorated murine colitis through the modulation of immune response, mucus barrier and gut microbiota, thus improving gut dysbiosis. In addition, the gut microbiota may play an important role in regulating the host's innate immune system, and the two coexist and are mutually beneficial. We provide a promising perspective on the clinical treatment of IBD.

Highlights

  • Ulcerative colitis (UC) is one form of inflammatory bowel disease (IBD) with a substantial impact on the quality of life of affected persons

  • The gut microbiota were analyzed by 16S rRNA sequencing and we performed fecal microbiota transplantation (FMT). It showed that TS ameliorated the colonic damage by lowering the disease activity index (DAI), prolonging the colon length, reducing inflammatory cytokines and improving the mucus barrier

  • Parallel to down-regulation of the inflammatory cytokines, the fecal lipocalin 2, p-P65, p-STAT3, and neutrophil accumulation were decreased in TS-treated mice

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Summary

Introduction

Ulcerative colitis (UC) is one form of IBD with a substantial impact on the quality of life of affected persons. The incidence of UC is high in Western developed countries but on the rise in China and other Asian countries in recent years [1, 2]. UC patients are more likely to develop colorectal cancer [3]. Numerous clinical data and animal experiments have demonstrated that UC is often accompanied with intestinal immunity dysfunction and imbalance of gut microbiota [4,5,6,7]. Dietary intervention is an exciting topic in current research of inflammatory bowel disease (IBD). We aim to investigate the intestinal anti-inflammatory activity of TS in a dextran sodium sulfate (DSS)-induced colitis mouse model and identify potential mechanisms

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