Dietary Salt Administration Decreases Enterotoxigenic <i>Bacteroides fragilis</i> (ETBF)-Promoted Tumorigenesis via Inhibition of Colonic Inflammation
Consumption of a Western-type diet has been linked to gut-microbiota-mediated colon inflammation that constitutes a risk factor for colorectal cancer. A high salt diet (HSD) exacerbates IL-17A-induced inflammation in inflammatory bowel disease and other autoimmune diseases. Enterotoxigenic <i>...
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MDPI AG
2020-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/21/8034 |
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| author | Soonjae Hwang Hye Chin Yi Samnoh Hwang Minjeong Jo Ki-Jong Rhee |
| author_facet | Soonjae Hwang Hye Chin Yi Samnoh Hwang Minjeong Jo Ki-Jong Rhee |
| author_sort | Soonjae Hwang |
| collection | DOAJ |
| description | Consumption of a Western-type diet has been linked to gut-microbiota-mediated colon inflammation that constitutes a risk factor for colorectal cancer. A high salt diet (HSD) exacerbates IL-17A-induced inflammation in inflammatory bowel disease and other autoimmune diseases. Enterotoxigenic <i>Bacteroides fragilis</i> (ETBF) is a gut commensal bacterium and reported to be a potent initiator of colitis via secretion of the <i>Bacteroides fragilis</i> toxin (BFT). BFT induces ectodomain cleavage of E-cadherin in colonic epithelial cells, consequently leading to cell rounding, epithelial barrier disruption, and the secretion of IL-8, which promotes tumorigenesis in mice via IL-17A-mediated inflammation. A HSD is characteristic of the Western-type diet and can exhibit inflammatory effects. However, a HSD induces effects in ETBF-induced colitis and tumorigenesis remain unknown. In this study, we investigated HSD effects in ETBF-colonized mice with azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced tumorigenesis as well as ETBF colitis mice. Unexpectedly, ETBF-infected mice fed a HSD exhibited decreased weight loss and splenomegaly and reduction of colon inflammation. The HSD significantly decreased the expression of IL-17A and inducible nitric oxide synthase (iNOS) in the colonic tissues of ETBF-infected mice. In addition, serum levels of IL-17A and nitric oxide (NO) were also diminished. However, HT29/C1 colonic epithelial cells treated with sodium chloride showed no changes in BFT-induced cellular rounding and IL-8 expression. Furthermore, HSD did not affect ETBF colonization in mice. In conclusion, HSD decreased ETBF-induced tumorigenesis through suppression of IL-17A and iNOS expression in the colon. HSD also inhibited colonic polyp numbers in the ETBF-infected AOM/DSS mice. Taken together, these findings suggest that a HSD consumption inhibited ETBF-promoted colon carcinogenesis in mice, indicating that a HSD could have beneficial effects under certain conditions. |
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| language | English |
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| spelling | doaj.art-23ad8c1883a64a9991ae42d6d264dcb12023-11-20T18:52:03ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-10-012121803410.3390/ijms21218034Dietary Salt Administration Decreases Enterotoxigenic <i>Bacteroides fragilis</i> (ETBF)-Promoted Tumorigenesis via Inhibition of Colonic InflammationSoonjae Hwang0Hye Chin Yi1Samnoh Hwang2Minjeong Jo3Ki-Jong Rhee4Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University MIRAE Campus, Wonju, Gangwon-do 26493, KoreaDepartment of Biomedical Laboratory Science, College of Health Sciences, Yonsei University MIRAE Campus, Wonju, Gangwon-do 26493, KoreaDepartment of Biomedical Laboratory Science, College of Health Sciences, Yonsei University MIRAE Campus, Wonju, Gangwon-do 26493, KoreaDepartment of Biomedical Laboratory Science, College of Health Sciences, Yonsei University MIRAE Campus, Wonju, Gangwon-do 26493, KoreaDepartment of Biomedical Laboratory Science, College of Health Sciences, Yonsei University MIRAE Campus, Wonju, Gangwon-do 26493, KoreaConsumption of a Western-type diet has been linked to gut-microbiota-mediated colon inflammation that constitutes a risk factor for colorectal cancer. A high salt diet (HSD) exacerbates IL-17A-induced inflammation in inflammatory bowel disease and other autoimmune diseases. Enterotoxigenic <i>Bacteroides fragilis</i> (ETBF) is a gut commensal bacterium and reported to be a potent initiator of colitis via secretion of the <i>Bacteroides fragilis</i> toxin (BFT). BFT induces ectodomain cleavage of E-cadherin in colonic epithelial cells, consequently leading to cell rounding, epithelial barrier disruption, and the secretion of IL-8, which promotes tumorigenesis in mice via IL-17A-mediated inflammation. A HSD is characteristic of the Western-type diet and can exhibit inflammatory effects. However, a HSD induces effects in ETBF-induced colitis and tumorigenesis remain unknown. In this study, we investigated HSD effects in ETBF-colonized mice with azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced tumorigenesis as well as ETBF colitis mice. Unexpectedly, ETBF-infected mice fed a HSD exhibited decreased weight loss and splenomegaly and reduction of colon inflammation. The HSD significantly decreased the expression of IL-17A and inducible nitric oxide synthase (iNOS) in the colonic tissues of ETBF-infected mice. In addition, serum levels of IL-17A and nitric oxide (NO) were also diminished. However, HT29/C1 colonic epithelial cells treated with sodium chloride showed no changes in BFT-induced cellular rounding and IL-8 expression. Furthermore, HSD did not affect ETBF colonization in mice. In conclusion, HSD decreased ETBF-induced tumorigenesis through suppression of IL-17A and iNOS expression in the colon. HSD also inhibited colonic polyp numbers in the ETBF-infected AOM/DSS mice. Taken together, these findings suggest that a HSD consumption inhibited ETBF-promoted colon carcinogenesis in mice, indicating that a HSD could have beneficial effects under certain conditions.https://www.mdpi.com/1422-0067/21/21/8034high salt dietenterotoxigenic <i>Bacteroides fragilis</i>tumorigenesis |
| spellingShingle | Soonjae Hwang Hye Chin Yi Samnoh Hwang Minjeong Jo Ki-Jong Rhee Dietary Salt Administration Decreases Enterotoxigenic <i>Bacteroides fragilis</i> (ETBF)-Promoted Tumorigenesis via Inhibition of Colonic Inflammation International Journal of Molecular Sciences high salt diet enterotoxigenic <i>Bacteroides fragilis</i> tumorigenesis |
| title | Dietary Salt Administration Decreases Enterotoxigenic <i>Bacteroides fragilis</i> (ETBF)-Promoted Tumorigenesis via Inhibition of Colonic Inflammation |
| title_full | Dietary Salt Administration Decreases Enterotoxigenic <i>Bacteroides fragilis</i> (ETBF)-Promoted Tumorigenesis via Inhibition of Colonic Inflammation |
| title_fullStr | Dietary Salt Administration Decreases Enterotoxigenic <i>Bacteroides fragilis</i> (ETBF)-Promoted Tumorigenesis via Inhibition of Colonic Inflammation |
| title_full_unstemmed | Dietary Salt Administration Decreases Enterotoxigenic <i>Bacteroides fragilis</i> (ETBF)-Promoted Tumorigenesis via Inhibition of Colonic Inflammation |
| title_short | Dietary Salt Administration Decreases Enterotoxigenic <i>Bacteroides fragilis</i> (ETBF)-Promoted Tumorigenesis via Inhibition of Colonic Inflammation |
| title_sort | dietary salt administration decreases enterotoxigenic i bacteroides fragilis i etbf promoted tumorigenesis via inhibition of colonic inflammation |
| topic | high salt diet enterotoxigenic <i>Bacteroides fragilis</i> tumorigenesis |
| url | https://www.mdpi.com/1422-0067/21/21/8034 |
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