Saccharomyces boulardii alleviates ulcerative colitis carcinogenesis in mice by reducing TNF-α and IL-6 levels and functions and by rebalancing intestinal microbiota

BMC Microbiol. 2019 Nov 6;19(1):246. doi: 10.1186/s12866-019-1610-8.

Abstract

Background and aims: To explore the inhibition mechanism of Saccharomyces boulardii (S. boulardii) on ulcerative colitis (UC) carcinogenesis.

Methods: C57BL/6 mice were treated with azoxymethane and dextran sulfate sodium (AOM/DSS) to develop a UC carcinogenesis model. The treatment group was lavaged with S. boulardii (5 × 107 CFU/d) for 12 weeks. The mice were sacrificed and the tumor load in the treatment group was compared with that of a control group. The levels of TNF-α and IL-6 in colon tissue were measured by enzyme-linked immunosorbent assays. The influence of S. boulardii on TNF-α and IL-6 regulation was also investigated using different colon cell lines. Differences in intestinal microbiota in both stool and intestinal mucosa samples were assessed using 16S rDNA sequencing.

Results: S. boulardii treatment reduced AOM/DSS-induced UC carcinogenesis in mice, as indicated by the reduced tumor load and reduced TNF-α and IL-6 levels in vivo, as well its effects on TNF-α and IL-6 activities in vitro. Significant changes in both fecal and mucosal microbiota were observed among the control, the AOM/DSS treated, and AOM/DSS plus S. boulardii treated groups. For fecal microbiota, the AOM/DSS treated group was lower in Lactobacillus, but higher in Oscillibacter and Lachnoclostridium than the control group. After intervention with S. boulardii, the percentage of Bacillus and Lactococcus increased, but Lachnoclostridium, Oscillibacter, Bacteroides, and Pseudomonas decreased. For the intestinal mucosal microbiota, the AOM/DSS treated group was lower in Bifidobacterium and Ruminococcaceae_UCG-014 and higher in Alloprevotella than the control group. After S. boulardii exposure, the percentage contributions of Lachnoclostridium and Lachnospiraceae_NK4A136 increased.

Conclusions: S. boulardii effectively reduced UC carcinogenesis in an AOM/DSS induced mice model. This positive result can likely be attributed to the reduction of TNF-α and IL-6 levels or the blockade of their function combined with alterations to the intestinal microbiota.

Keywords: IL-6; Intestinal microbiota; Saccharomyces boulardii; TNF-α; Ulcerative colitis carcinogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Azoxymethane / adverse effects
  • Bacteria / classification*
  • Bacteria / genetics
  • Bacteria / isolation & purification
  • Caco-2 Cells
  • Cell Line, Tumor
  • Colitis, Ulcerative / chemically induced
  • Colitis, Ulcerative / complications
  • Colitis, Ulcerative / immunology
  • Colitis, Ulcerative / therapy*
  • Colonic Neoplasms / etiology
  • Colonic Neoplasms / immunology
  • Colonic Neoplasms / therapy*
  • Dextran Sulfate / adverse effects
  • Disease Models, Animal
  • Down-Regulation
  • Feces / microbiology
  • Gastrointestinal Microbiome
  • Gene Expression Regulation, Neoplastic
  • HCT116 Cells
  • Humans
  • Interleukin-6 / metabolism*
  • Intestinal Mucosa / microbiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Saccharomyces boulardii / physiology*
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Interleukin-6
  • Tnf protein, mouse
  • Tumor Necrosis Factor-alpha
  • interleukin-6, mouse
  • Dextran Sulfate
  • Azoxymethane