Treatment and mechanism of fecal microbiota transplantation in mice with experimentally induced ulcerative colitis

Exp Biol Med (Maywood). 2021 Jul;246(13):1563-1575. doi: 10.1177/15353702211006044. Epub 2021 Apr 29.

Abstract

Restoring intestinal microbiota dysbiosis with fecal microbiota transplantation is considered as a promising treatment for ulcerative colitis. However, the mechanisms underlying its relieving effects remain unclear. Ulcerative colitis pathogenesis is associated with the involvement of immune cells and inflammatory cytokines. Here, we aimed to investigate the effect of fecal microbiota transplantation on T cell cytokines in a dextran sulfate sodium-induced ulcerative colitis mouse model. Five-aminosalicylic acid (5-ASA) was used as the positive control. Male C57BL/6 mice were randomly assigned to control, model (UC), UC + FMT, and UC + 5-ASA groups. Each group consisted of five mice. The establishment of the mouse model was verified by fecal occult-blood screening and hematoxylin-eosin staining. Results showed that fecal microbiota transplantation reduced colonic inflammation, significantly decreased T helper (Th)1 and Th17 cells, interferon-gamma, interleukin-2 and interleukin-17, as well as significantly increased Th2 and regulatory T (Treg) cells, interleukin-4, interleukin-10, and transforming growth factor-beta, and improved routine blood count. Furthermore, 16S rRNA gene-sequencing analysis showed a significant increase in the relative abundance of genus Akkermansia and a significant decrease in the relative abundance of genus Helicobacter in the ulcerative colitis group. Fecal microbiota transplantation restored the profile of the intestinal microbiota to that of the control group. These findings demonstrated the capability of fecal microbiota transplantation in controlling experimentally induced ulcerative colitis by improving Th1/Th2 and Th17/Treg imbalance through the regulation of intestinal microbiota.

Keywords: 5-aminosalicylic acid; Fecal microbiota transplantation; Th1/Th2; Th17/Treg; microbial diversity; ulcerative colitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Akkermansia / isolation & purification
  • Akkermansia / pathogenicity
  • Animals
  • Colitis, Ulcerative / etiology
  • Colitis, Ulcerative / microbiology
  • Colitis, Ulcerative / therapy*
  • Colon / metabolism
  • Colon / microbiology
  • Dextran Sulfate / toxicity
  • Fecal Microbiota Transplantation / methods*
  • Gastrointestinal Microbiome*
  • Helicobacter / isolation & purification
  • Helicobacter / pathogenicity
  • Interleukins / genetics
  • Interleukins / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • T-Lymphocytes / metabolism
  • Transforming Growth Factor beta / metabolism

Substances

  • Interleukins
  • Transforming Growth Factor beta
  • Dextran Sulfate