Abstract

Increasingly studies revealed that dysbiosis of gut microbiota plays a pivotal role in the pathogenesis of ulcerative colitis (UC). Fecal microbiota transplantation (FMT) has drawn more and more attention and become an important therapeutic approach. This study aims to examine the facts about the effective components and look into potential mechanisms of FMT. Colitis was induced by 3% (w/v) dextran sulfate sodium (DSS) in drinking water for 7 days. Colitis mice were administered by oral gavage with fecal suspension, fecal supernatant, fecal bacteria, or boiling-killed fecal bacteria from healthy controls and the disease activity index was monitored daily. On the seventh day, mice were euthanized. The length, histological score, parameters related to inflammation, gut barrier functions of the colon, activities of digestive protease and β-glucuronidase in feces were measured. All of the four fecal components showed certain degree of efficacy in DSS-induced colitis, while transplantation of fecal suspension showed the most potent effect as demonstrated by less body weight loss, lower disease activity scores, more expression of tight junction proteins and TRAF6 and IκBα, less expression of TNF-α, IL-1β, IL-10, TLR-4, and MyD88 in gut tissue, as well as restoration of fecal β-glucuronidase and decreases in fecal digestive proteases. These results provide a novel insight into the possible mechanism of FMT and may help to improve and optimize clinical use of FMT.

Highlights

  • Ulcerative colitis (UC) is one of the main forms of inflammatory bowel disease (IBD) with unknown etiology, mainly characterized as non-specific inflammation of the rectum and colon (Ordás et al, 2012)

  • The results showed that four different component of fecal microbiota transplantation (FMT) all exerted some degrees of inhibition on dextran sulfate sodium (DSS)-induced colitis as exhibited by the less body weight loss, lower disease scores, and less shortening of colons, less anal bleeding, less inflammation manifestation, and less histological scores (Figures 1A–F), Among them, transplantation of fecal suspension showed the most potent efficacy on the relief of colitis

  • As DSS and FMT began at the same time, our results suggest that this intervention may have both prevention and treatment effects on colitis

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Summary

Introduction

Ulcerative colitis (UC) is one of the main forms of inflammatory bowel disease (IBD) with unknown etiology, mainly characterized as non-specific inflammation of the rectum and colon (Ordás et al, 2012). It emerged for only about a century and has kept increasing worldwide, as shown by the remarkable increase in recent years in Asia (Ng et al, 2015; Bernstein, 2017; Kaplan and Ng, 2017). Multiple studies have demonstrated therapeutic effect of FMT on UC (Costello et al, 2017; D’Odorico et al, 2018), but the specific functional component and mechanism remains to be elucidated

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