Abstract | BACKGROUND AND AIM: METHODS: RESULTS: Mice consuming inulin-containing diet exhibited severe colitis upon DSS administration, as evidenced by more body weight loss, rectal bleeding, and increased colonic inflammation than the DSS-treated control group. Correspondingly, histological analysis revealed extensive disruption of colon architecture and massive infiltration of immune cells in the inulin-fed group. We next examined the effect of inulin on CRC development. Surprisingly, significant mortality (~50%) was observed in the inulin-fed but not in the control group during the DSS cycle. Consequently, the remaining inulin-fed mice, which completed the study exhibited extensive colon tumorigenesis. Immunohistochemical characterization showed comparatively high expression of the cell proliferation marker Ki67 and activation of the Wnt signaling in tumor sections obtained from the inulin-fed group. Gut microbiota and metabolite analysis revealed expansion of succinate producers and elevated cecal succinate in inulin-fed mice. Human colorectal carcinoma cells (HCT116) proliferated more rapidly when supplemented with succinate in an inflamed environment, suggesting that elevated luminal succinate may contribute to tumorigenesis. CONCLUSIONS: Our study uncovers that supplementation of diet with refined inulin induces abnormal succinate accumulation in the intestinal lumen, which in part contributes to promoting colon inflammation and tumorigenesis.
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Authors | Sangshan Tian, Devendra Paudel, Fuhua Hao, Rabin Neupane, Rita Castro, Andrew D Patterson, Amit K Tiwari, K Sandeep Prabhu, Vishal Singh |
Journal | Cancer reports (Hoboken, N.J.)
(Cancer Rep (Hoboken))
Vol. 6
Issue 11
Pg. e1863
(11 2023)
ISSN: 2573-8348 [Electronic] United States |
PMID | 37489647
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't)
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Copyright | © 2023 The Authors. Cancer Reports published by Wiley Periodicals LLC. |
Chemical References |
- Inulin
- Succinic Acid
- Dextran Sulfate
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Topics |
- Humans
- Animals
- Mice
- Inulin
- Succinic Acid
- Dextran Sulfate
(toxicity)
- Inflammation
(complications, pathology)
- Colitis
(complications, metabolism, pathology)
- Colonic Neoplasms
(chemically induced)
- Colorectal Neoplasms
(chemically induced)
- Carcinogenesis
- Cell Transformation, Neoplastic
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