Toll-like receptor 4 prevents AOM/DSS-induced colitis-associated colorectal cancer in Bacteroides fragilis gnotobiotic mice

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

Research output: Contribution to journalArticlepeer-review

Abstract

Bacteroides fragilis (BF) plays a critical role in developing and maintaining the mammalian immune system. We previously found that BF colonization could prevent inflammation and tumor formation in a germ-free (GF) colitis-associated colorectal cancer (CAC) mouse model. The role of Toll-like receptor 4 (TLR4) in CAC development has not been clearly elucidated in BF mono-colonized gnotobiotic mice. The wild-type (WT) and TLR4 knockout (T4K) germ-free mice were raised with or without BF colonization for 28 days (GF/WT, GF/T4K, BF/WT, and BF/T4K) and then CAC was induced under azoxymethane (AOM)/dextran sulfate sodium (DSS) administration. The results showed that tumor formation and tumor incidence were significantly inhibited in the BF/WT group compared to those observed in the GF/WT group. However, the tumor prevention effect was not observed in the BF/T4K group unlike in the BF/WT group. Moreover, the CAC histological severity of the BF/WT group was ameliorated, but more severe lesions were found in the GF/WT, GF/T4K, and BF/T4K groups. Immunohistochemistry showed decreased cell proliferation (PCNA, β-catenin) and inflammatory markers (iNOS) in the BF/WT group compared to those in the BF/T4K group. Taken together, BF mono-colonization of GF mice might prevent CAC via the TLR4 signal pathway.

Original languageEnglish
JournalHuman and Experimental Toxicology
DOIs
Publication statusAccepted/In press - 2020

Keywords

  • Bacteroides fragilis
  • colitis-associated colorectal cancer
  • gnotobiotic
  • mono-colonization
  • Toll-like receptor 4

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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