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

Yen Peng Lee, Chien Chao Chiu, Tien Jen Lin, Shao Wen Hung, Wen Ching Huang, Ching Feng Chiu, Yen Te Huang, Yi Hsun Chen, Ter Hsin Chen, Hsiao Li Chuang

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalImmunopharmacology and Immunotoxicology
DOIs
Publication statusPublished - Jan 1 2019

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Azoxymethane
Bacteroides fragilis
Dextran Sulfate
Colitis
Colorectal Neoplasms
Cell proliferation
Tumors
Cecum
Catenins
Proliferating Cell Nuclear Antigen
Infiltration
Cell Proliferation
Staining and Labeling
Bacteria
Animals
Incidence
Inflammatory Bowel Diseases
Granulocytes
Adenoma
Molecules

Keywords

  • anti-tumorigenesis
  • AOM
  • BF
  • CAC
  • DSS

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Toxicology
  • Pharmacology

Cite this

The germ-free mice monocolonization with Bacteroides fragilis improves azoxymethane/dextran sulfate sodium induced colitis-associated colorectal cancer. / Lee, Yen Peng; Chiu, Chien Chao; Lin, Tien Jen; Hung, Shao Wen; Huang, Wen Ching; Chiu, Ching Feng; Huang, Yen Te; Chen, Yi Hsun; Chen, Ter Hsin; Chuang, Hsiao Li.

In: Immunopharmacology and Immunotoxicology, 01.01.2019.

Research output: Contribution to journalArticle

Lee, Yen Peng ; Chiu, Chien Chao ; Lin, Tien Jen ; Hung, Shao Wen ; Huang, Wen Ching ; Chiu, Ching Feng ; Huang, Yen Te ; Chen, Yi Hsun ; Chen, Ter Hsin ; Chuang, Hsiao Li. / The germ-free mice monocolonization with Bacteroides fragilis improves azoxymethane/dextran sulfate sodium induced colitis-associated colorectal cancer. In: Immunopharmacology and Immunotoxicology. 2019.
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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.",
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T1 - The germ-free mice monocolonization with Bacteroides fragilis improves azoxymethane/dextran sulfate sodium induced colitis-associated colorectal cancer

AU - Lee, Yen Peng

AU - Chiu, Chien Chao

AU - Lin, Tien Jen

AU - Hung, Shao Wen

AU - Huang, Wen Ching

AU - Chiu, Ching Feng

AU - Huang, Yen Te

AU - Chen, Yi Hsun

AU - Chen, Ter Hsin

AU - Chuang, Hsiao Li

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - anti-tumorigenesis

KW - AOM

KW - BF

KW - CAC

KW - DSS

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