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Refined fiber inulin promotes inflammation‐associated colon tumorigenesis by modulating microbial succinate production
BACKGROUND AND AIM: There is an increased risk of colon cancer associated with inflammatory bowel disease (IBD). Dietary fibers (DFs) naturally present in vegetables and whole grains offer numerous beneficial effects on intestinal health. However, the effects of refined DFs on intestinal health rema...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10644334/ https://www.ncbi.nlm.nih.gov/pubmed/37489647 http://dx.doi.org/10.1002/cnr2.1863 |
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author | Tian, Sangshan Paudel, Devendra Hao, Fuhua Neupane, Rabin Castro, Rita Patterson, Andrew D. Tiwari, Amit K. Prabhu, K. Sandeep Singh, Vishal |
author_facet | Tian, Sangshan Paudel, Devendra Hao, Fuhua Neupane, Rabin Castro, Rita Patterson, Andrew D. Tiwari, Amit K. Prabhu, K. Sandeep Singh, Vishal |
author_sort | Tian, Sangshan |
collection | PubMed |
description | BACKGROUND AND AIM: There is an increased risk of colon cancer associated with inflammatory bowel disease (IBD). Dietary fibers (DFs) naturally present in vegetables and whole grains offer numerous beneficial effects on intestinal health. However, the effects of refined DFs on intestinal health remain unclear. Therefore, we elucidated the impact of the refined DF inulin on colonic inflammation and tumorigenesis. METHODS: Four‐week‐old wild‐type (WT) mice were fed diets containing insoluble DF cellulose (control) or refined DF inulin for 4 weeks. A subgroup of mice was then switched to drinking water containing dextran sulfate sodium (DSS, 1.4% wt/vol) for colitis induction. In another subgroup of mice, colitis‐associated colorectal cancer (CRC) was initiated with three 7‐day alternate cycles of DSS following an initial dose of mutagenic substance azoxymethane (AOM; 7.5 mg/kg body weight; i.p.). Post 7 weeks of AOM treatment, mice were euthanized and examined for CRC development. 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. |
format | Online Article Text |
id | pubmed-10644334 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-106443342023-11-15 Refined fiber inulin promotes inflammation‐associated colon tumorigenesis by modulating microbial succinate production Tian, Sangshan Paudel, Devendra Hao, Fuhua Neupane, Rabin Castro, Rita Patterson, Andrew D. Tiwari, Amit K. Prabhu, K. Sandeep Singh, Vishal Cancer Rep (Hoboken) Original Article BACKGROUND AND AIM: There is an increased risk of colon cancer associated with inflammatory bowel disease (IBD). Dietary fibers (DFs) naturally present in vegetables and whole grains offer numerous beneficial effects on intestinal health. However, the effects of refined DFs on intestinal health remain unclear. Therefore, we elucidated the impact of the refined DF inulin on colonic inflammation and tumorigenesis. METHODS: Four‐week‐old wild‐type (WT) mice were fed diets containing insoluble DF cellulose (control) or refined DF inulin for 4 weeks. A subgroup of mice was then switched to drinking water containing dextran sulfate sodium (DSS, 1.4% wt/vol) for colitis induction. In another subgroup of mice, colitis‐associated colorectal cancer (CRC) was initiated with three 7‐day alternate cycles of DSS following an initial dose of mutagenic substance azoxymethane (AOM; 7.5 mg/kg body weight; i.p.). Post 7 weeks of AOM treatment, mice were euthanized and examined for CRC development. 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. John Wiley and Sons Inc. 2023-07-25 /pmc/articles/PMC10644334/ /pubmed/37489647 http://dx.doi.org/10.1002/cnr2.1863 Text en © 2023 The Authors. Cancer Reports published by Wiley Periodicals LLC. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Tian, Sangshan Paudel, Devendra Hao, Fuhua Neupane, Rabin Castro, Rita Patterson, Andrew D. Tiwari, Amit K. Prabhu, K. Sandeep Singh, Vishal Refined fiber inulin promotes inflammation‐associated colon tumorigenesis by modulating microbial succinate production |
title | Refined fiber inulin promotes inflammation‐associated colon tumorigenesis by modulating microbial succinate production |
title_full | Refined fiber inulin promotes inflammation‐associated colon tumorigenesis by modulating microbial succinate production |
title_fullStr | Refined fiber inulin promotes inflammation‐associated colon tumorigenesis by modulating microbial succinate production |
title_full_unstemmed | Refined fiber inulin promotes inflammation‐associated colon tumorigenesis by modulating microbial succinate production |
title_short | Refined fiber inulin promotes inflammation‐associated colon tumorigenesis by modulating microbial succinate production |
title_sort | refined fiber inulin promotes inflammation‐associated colon tumorigenesis by modulating microbial succinate production |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10644334/ https://www.ncbi.nlm.nih.gov/pubmed/37489647 http://dx.doi.org/10.1002/cnr2.1863 |
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