Pretreatment with probiotic Bifico ameliorates colitis-associated cancer in mice: Transcriptome and gut flora profiling

Cancer Sci. 2018 Mar;109(3):666-677. doi: 10.1111/cas.13497. Epub 2018 Feb 14.

Abstract

Individuals with inflammatory bowel disease are at high risk of developing colitis-associated cancer (CAC). Strategies to block the process from inflammatory bowel disease to CAC should be considered. In the experiment, we aim to explore the chemopreventive efficacy of the probiotic cocktail Bifico and its potential mechanism in azoxymethane and dextran sodium sulphate-induced CAC in mice. Oral pretreatment of Bifico was adopted to evaluate its protective effect. The colorectums of 35 C57BL/6 mice were collected and examined for the degree of inflammation and tumorigenesis. Comparative 16S rRNA sequencing was carried out to observe Bifico-target alterations in gene expression and microbiota structure. We found that pretreatment of Bifico alleviated intestinal inflammation and reduced tumor formation. Furthermore, we identified a subset of genes as potential targets of Bifico treatment, including CXCL1, CXCL2, CXCL3, and CXCL5, which are all ligands of C-X-C motif receptor 2 (CXCR2). The 16S rRNA sequencing showed that Bifico decreased the abundance of genera Desulfovibrio, Mucispirillum, and Odoribacter, and a bloom of genus Lactobacillus was detected. Notably, we found that an abundance of these Bifico-target taxa was significantly associated with the expression of CXCR2 ligand genes. Our studies indicate that Bifico, given orally, can ameliorate CAC in mice through intervening with the possible link between Desulfovibrio, Mucispirillum, Odoribacter, Lactobacillus, and CXCR2 signaling.

Keywords: carcinogenesis; chemokines; colorectal neoplasms; gastrointestinal microbiome.

MeSH terms

  • Administration, Oral
  • Animals
  • Azoxymethane
  • Bacteria / classification*
  • Bacteria / drug effects*
  • Bacteria / genetics
  • Chemokines, CXC / genetics
  • Colitis / chemically induced*
  • Colitis / complications
  • Colitis / genetics
  • Colorectal Neoplasms / chemically induced
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Dextran Sulfate
  • Disease Models, Animal
  • Gastrointestinal Microbiome / drug effects
  • Gene Expression Profiling / methods*
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Probiotics / administration & dosage*
  • Probiotics / pharmacology
  • RNA, Ribosomal, 16S / genetics
  • Signal Transduction
  • Xenograft Model Antitumor Assays

Substances

  • Chemokines, CXC
  • RNA, Ribosomal, 16S
  • Dextran Sulfate
  • Azoxymethane