Abstract

BackgroundAlteration of the gut microbiota may contribute to the development of inflammatory bowel disease (IBD). Epigallocatechin-3-gallate (EGCG), a major bioactive constituent of green tea, is known to be beneficial in IBD alleviation. However, it is unclear whether the gut microbiota exerts an effect when EGCG attenuates IBD.ResultsWe first explored the effect of oral or rectal EGCG delivery on the DSS-induced murine colitis. Our results revealed that anti-inflammatory effect and colonic barrier integrity were enhanced by oral, but not rectal, EGCG. We observed a distinct EGCG-mediated alteration in the gut microbiome by increasing Akkermansia abundance and butyrate production. Next, we demonstrated that the EGCG pre-supplementation induced similar beneficial outcomes to oral EGCG administration. Prophylactic EGCG attenuated colitis and significantly enriched short-chain fatty acids (SCFAs)-producing bacteria such as Akkermansia and SCFAs production in DSS-induced mice. To validate these discoveries, we performed fecal microbiota transplantation (FMT) and sterile fecal filtrate (SFF) to inoculate DSS-treated mice. Microbiota from EGCG-dosed mice alleviated the colitis over microbiota from control mice and SFF shown by superiorly anti-inflammatory effect and colonic barrier integrity, and also enriched bacteria such as Akkermansia and SCFAs. Collectively, the attenuation of colitis by oral EGCG suggests an intimate involvement of SCFAs-producing bacteria Akkermansia, and SCFAs, which was further demonstrated by prophylaxis and FMT.ConclusionsThis study provides the first data indicating that oral EGCG ameliorated the colonic inflammation in a gut microbiota-dependent manner. Our findings provide novel insights into EGCG-mediated remission of IBD and EGCG as a potential modulator for gut microbiota to prevent and treat IBD.1weu4UfF6nDLmdPiHVjMmdVideo

Highlights

  • IntroductionInflammatory bowel diseases (IBD), clinically consisting of ulcerative colitis and Crohn’s disease, are chronic inflammatory diseases of the gastrointestinal tract [1]

  • Inflammatory bowel diseases (IBD), clinically consisting of ulcerative colitis and Crohn’s disease, are chronic inflammatory diseases of the gastrointestinal tract [1].They are becoming more prevalent worldwide in recent years [2]

  • But not rectal EGCG administration alleviated dextran sulfate sodium (DSS)‐induced colitis To study the alleviated effect of EGCG on DSS-induced colitis, experimental colitis was induced in mice by administering 2.5% DSS in water continuously for 7 days, followed by 3 days of daily oral (Fig. 2a) or rectal delivery (Figure S1a) of 50 mg/kg body weight EGCG, based on the optimal dose that we have observed previously

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Summary

Introduction

Inflammatory bowel diseases (IBD), clinically consisting of ulcerative colitis and Crohn’s disease, are chronic inflammatory diseases of the gastrointestinal tract [1]. They are becoming more prevalent worldwide in recent years [2]. Numerous epidemiological evidences support that daily diets impact the risk in chronic diseases such as IBD [10, 11]; it is still unclear whether it is mediated by changes in microbiota composition. Epigallocatechin-3-gallate (EGCG), a major bioactive constituent of green tea, is known to be beneficial in IBD alleviation. It is unclear whether the gut microbiota exerts an effect when EGCG attenuates IBD

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