DSS colitis promotes tumorigenesis and fibrogenesis in a choline-deficient high-fat diet-induced NASH mouse model
Abstract
Nonalcoholic steatohepatitis (NASH) patients progress to liver cirrhosis and even hepatocellular carcinoma (HCC). Several lines of evidence indicate that accumulation of lipopolysaccharide (LPS) and disruption of gut microbiota play contributory roles in HCC. Moreover, in a dextran sodium sulfate (DSS)-induced colitis model in mice, a high-fat diet increases portal LPS level and promotes hepatic inflammation and fibrosis. However, this diet-induced NASH model requires at least 50 weeks for carcinogenesis. In this study, we sought to determine whether increased intestinal permeability would aggravate liver inflammation and fibrosis and accelerate tumorigenesis in a diet-induced NASH model. Mice were fed a choline-deficient high-fat (CDHF) diet for 4 or 12 weeks. The DSS group was fed CDHF and intermittently received 1% DSS in the drinking water. Exposure to DSS promoted mucosal changes such as crypt loss and increased the number of inflammatory cells in the colon. In the DSS group, portal LPS levels were elevated at 4 weeks, and the proportions of Clostridium cluster XI in the fecal microbiota were elevated. In addition, levels of serum transaminase, number of lobular inflammatory cells, F4/80 staining-positive area, and levels of inflammatory cytokines were all elevated in the DSS group. Liver histology in the DSS group revealed severe fibrosis at 12 weeks. Liver tumors were detected in the DSS group at 12 weeks, but not in the other groups. Thus, DSS administration promoted liver tumors in a CDHF diet-induced NASH mouse over the short term, suggesting that the induction of intestinal inflammation and gut disruption of microbiota in NASH promote hepatic tumorigenesis.
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Disruption of the gut barrier by dextran sulfate sodium increases systemic lipopolysaccharide levels and liver fibrosis and promotes hepatocellular carcinoma formation in mice.
“Likewise, disruption of the gut barrier by administration of dextran sulfate sodium not only results in increased systemic LPS levels and increased liver fibrosis, but also promotes HCC formation in mice80,81.”
From The gut microbiome and liver cancer: mechanisms and clinical translation (2017) · cites this paper as [81]
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- Authors
- Achiwa, K., Ishigami, M., Ishizu, Y., Kuzuya, T., Honda, T., Hayashi, K., Hirooka, Y., Katano, Y., & Goto, H.
- Affiliations
- Nagoya University (JP)
- Fujita Health University (JP)
- Corresponding author
- Ishigami, Masatoshi
- ORCID
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2016-01
- Volume
- 470
- Issue
- 1
- Pages
- 15-21
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2193870351
- Cited by
- 54
- References
- 32
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 9 · 2023: 5 · 2022: 4 · 2021: 11 · 2020: 7 · 2019: 6 · 2018: 3 · 2017: 3 · 2016: 1
- FWCI
- 1.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- nonalcoholic steatohepatitis, DSS-induced colitis, choline-deficient high-fat diet, hepatocellular carcinoma, liver fibrosis, intestinal permeability, lipopolysaccharide, gut microbiota, intestinal inflammation, liver inflammation, carcinogenesis, gut-liver axis
- MeSH terms
- Gastrointestinal Microbiome, Animals, Choline Deficiency, Colitis, Intestinal Absorption, Liver Cirrhosis, Male, Mice, Inbred C57BL, Dextran Sulfate, Mice, Diet, High-Fat, Carcinogenesis, Non-alcoholic Fatty Liver Disease
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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