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Toll-Like Receptor 2-Mediated Suppression of Colorectal Cancer Pathogenesis by Polysaccharide A From Bacteroides fragilis.

ABSTRACT: The beneficial role of gut microbiota in intestinal diseases has been highlighted recently. Bacteroides fragilis found in the human gastrointestinal tract is a well-studied example of a beneficial bacterium that protects against intestinal inflammation. Polysaccharide A (PSA) from B. fragilis induces the production of interleukin (IL)-10 from immune cells via Toll-like receptor 2 (TLR2) signaling in animal colitis models. The direct effect of PSA on human colorectal cancer (CRC) cells has not been studied. Here, we report the effect of PSA from B. fragilis on CRC pathogenesis in SW620 and HT29 CRC cells and the molecular signaling underlying these effects. We demonstrated that PSA induced the production of the pro-inflammatory cytokine, IL-8, but not IL-10, in CRC cells. PSA inhibited CRC cell proliferation by controlling the cell cycle and impaired CRC cell migration and invasion by suppressing epithelial mesenchymal transition. Moreover, as in the case of other animal intestinal diseases, the protective role of PSA against CRC pathogenesis was also mediated by TLR2. Our results reveal that PSA from B. fragilis plays a protective role against CRC via TLR2 signaling.

SUBMITTER: Sittipo P

PROVIDER: S-EPMC6056687 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Toll-Like Receptor 2-Mediated Suppression of Colorectal Cancer Pathogenesis by Polysaccharide A From Bacteroides fragilis.

Sittipo Panida P Lobionda Stefani S Choi Kyungchul K Sari Ita Novita IN Kwon Hyog Young HY Lee Yun Kyung YK

Frontiers in microbiology 20180717

The beneficial role of gut microbiota in intestinal diseases has been highlighted recently. Bacteroides fragilis found in the human gastrointestinal tract is a well-studied example of a beneficial bacterium that protects against intestinal inflammation. Polysaccharide A (PSA) from B. fragilis induces the production of interleukin (IL)-10 from immune cells via Toll-like receptor 2 (TLR2) signaling in animal colitis models. The direct effect of PSA on human colorectal cancer (CRC) ce ...[more]

PMID: 30065713

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Project description:To evaluate the impact of recombinant Bacteroides fragilis enterotoxin-2 (BFT-2, or Fragilysin) on colorectal tumorigenesis in mice induced by azoxymethane/dextran sulfate sodium (AOM/DSS).Recombinant proBFT-2 was expressed in Escherichia coli strain Rosetta (DE3) and BFT-2 was obtained and tested for its biological activity via colorectal adenocarcinoma cell strains SW-480. Seventy C57BL/6J mice were randomly divided into a blank (BC; n = 10), model (AD; n = 20), model + low-dose toxin (ADLT; n = 20, 10 ?g), and a model + high-dose toxin (ADHT; n = 20, 20 ?g) group. Mice weight, tumor formation and pathology were analyzed. Immunohistochemistry determined Ki-67 and Caspase-3 expression in normal and tumor tissues of colorectal mucosa.Recombinant BFT-2 was successfully obtained, along with its biological activity. The most obvious weight loss occurred in the AD group compared with the ADLT group (21.82 ± 0.68 vs 23.23 ± 0.91, P < 0.05) and the ADHT group (21.82 ± 0.68 vs 23.57 ± 1.06, P < 0.05). More tumors were found in the AD group than in the ADLT and ADHT groups (19.75 ± 3.30 vs 6.50 ± 1.73, P < 0.05; 19.75 ± 3.30 vs 6.00 ± 2.16, P < 0.05). Pathology showed that 12 mice had adenocarcinoma and 6 cases had adenoma in the AD group. Five mice had adenocarcinoma and 15 had adenoma in the ADLT group. Four mice had adenocarcinoma and 16 had adenoma in the ADHT group. The incidence of colorectal adenocarcinoma in both the ADHT group and the ADHT group was reduced compared to that in the AD group (P < 0.05, P < 0.05). The positive rate of Ki-67 in the ADLT group and the ADHT group was 50% and 40%, respectively, both of which were lower than that found in the AD group (94.44%, P < 0.05, P < 0.05). Caspase-3 expression in the ADLT group and the ADHT group was 45% and 55%, both of which were higher than that found in the BC group (16.67%, P < 0.05, P < 0.05).Oral administration with lower-dose biologically active recombinant BFT-2 inhibited colorectal tumorigenesis in mice.

Dataset Information

Toll-Like Receptor 2-Mediated Suppression of Colorectal Cancer Pathogenesis by Polysaccharide A From Bacteroides fragilis.

Publications

Toll-Like Receptor 2-Mediated Suppression of Colorectal Cancer Pathogenesis by Polysaccharide A From <i>Bacteroides fragilis</i>.

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