The Protective Role of Bacteroides fragilis in a Murine Model of Colitis-Associated Colorectal Cancer

Author:

Lee Yun Kyung12,Mehrabian Parpi1,Boyajian Silva1,Wu Wei-Li13,Selicha Jane1,Vonderfecht Steven4,Mazmanian Sarkis K.1

Affiliation:

1. Division of Biology & Biological Engineering, California Institute of Technology, Pasadena, California, USA

2. Soonchunhyang Institute of Medi-Bio Science, Soonchunhyang University, Cheonan, Republic of Korea

3. Department of Physiology, College of Medicine, National Cheng Kung University, Tainan, Taiwan

4. Center for Comparative Medicine, Beckman Research Institute, City of Hope, Duarte, California, USA

Abstract

The incidence of colorectal cancer (CRC) is rapidly growing worldwide, and there is therefore a greater emphasis on studies of the treatment or prevention of CRC pathogenesis. Recent studies suggested that consideration of the microbiota is unavoidable to understand inflammation and tumorigenesis in the gastrointestinal tract. We demonstrate, using a mouse model of colitis-associated CRC, that human commensal B. fragilis protects against colon tumorigenesis. The protective role against tumor formation provided by B. fragilis is associated with inhibition of expression of the chemokine receptor CCR5 in the colon. The molecular mechanism for protection against CRC provided by B. fragilis is dependent on polysaccharide A production and is mediated by TLR2 signaling. Our results suggest that the commensal microorganism B. fragilis can be used to prevent inflammation-associated CRC development and may provide an effective therapeutic strategy for CRC.

Funder

HHS | National Institutes of Health

National Research Foundation of Korea

Publisher

American Society for Microbiology

Subject

Molecular Biology,Microbiology

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