The germ-free mice monocolonization with Bacteroides fragilis improves azoxymethane/dextran sulfate sodium induced colitis-associated colorectal cancer

Immunopharmacol Immunotoxicol. 2019 Apr;41(2):207-213. doi: 10.1080/08923973.2019.1569047. Epub 2019 Feb 1.

Abstract

Objective: Inflammatory bowel disease (IBD) is generally considered as a major risk factor in the progression of colitis-associated colorectal cancer (CAC). Previous studies have indicated that the composition of gut microflora may be involved in CAC induction and progress. Bacteroides fragilis (BF) is a Gram-negative anaerobe belonging to colonic symbiotic bacteria of the host. This study was aimed to investigate the protective role of BF in a colorectal cancer (CRC) model induced by azoxymethane (AOM) and dextran sulfate sodium (DSS) in germ-free (GF) mice. Materials and methods: Total 22 GF mice were divided into two groups: GF and BF group. Half of the GF mice were colonized with BF for 28 days before CRC induction by AOM/DSS. Results: BF colonization increased animal survival (100%). Cecum weight and cecum/body weight ratio significantly decreased in BF/AOM/DSS group. Interestingly, there was a significant decrease in tumor number and tumor incidence in the BF/AOM/DSS group as compared to the GF/AOM/DSS group. The adenocarcinoma/adenoma incidence and histologic score were also decreased in the BF/AOM/DSS group. In addition, immunohistochemistry staining found decreased numbers of cell proliferation (PCNA) and inflammatory cell (granulocytes) infiltration in the colon mucosa of the BF group. The β-catenin staining in the BF/AOM/DSS group had fewer and weaker positive signal expressions. Taking together, the BF colonization significantly ameliorated AOM/DSS-induced CRC by suppressing the activity of cell proliferation-related molecules and reducing the number of inflammatory cells. Conclusions: Symbiotic BF may play a pivotal role in maintaining the gastrointestinal immunophysiologic balance and regulating anti-tumorigenesis responses.

Keywords: AOM; BF; CAC; DSS; anti-tumorigenesis.

MeSH terms

  • Animals
  • Azoxymethane / toxicity*
  • Bacteroides fragilis / immunology*
  • Colitis* / chemically induced
  • Colitis* / immunology
  • Colitis* / pathology
  • Colitis* / prevention & control
  • Colorectal Neoplasms* / chemically induced
  • Colorectal Neoplasms* / immunology
  • Colorectal Neoplasms* / pathology
  • Colorectal Neoplasms* / prevention & control
  • Dextran Sulfate / toxicity*
  • Germ-Free Life*
  • Male
  • Mice

Substances

  • Dextran Sulfate
  • Azoxymethane