Hereditary hemochromatosis promotes colitis and colon cancer and causes bacterial dysbiosis in mice
| العنوان: | Hereditary hemochromatosis promotes colitis and colon cancer and causes bacterial dysbiosis in mice |
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| المؤلفون: | Abdul N. Hamood, Kameswara Rao Kottapalli, Vadivel Ganapathy, Jane A. Colmer-Hamood, Bojana Ristic, Sathish Sivaprakasam, Anna G. Nevels, Mitchell S. Wachtel, Nithya S. Mudaliar |
| المصدر: | Biochemical Journal |
| بيانات النشر: | Portland Press Ltd., 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Colorectal cancer, colitis, Antimicrobial peptides, Inflammation, Biochemistry, hemochromatosis, 03 medical and health sciences, Mice, 0302 clinical medicine, Proteobacteria, medicine, Animals, Microbiome, Colitis, Hemochromatosis Protein, Molecular Biology, Hemochromatosis, Research Articles, 030304 developmental biology, Cancer, Mice, Knockout, 0303 health sciences, business.industry, iron/heme overload, Cell Biology, dysbiosis, medicine.disease, digestive system diseases, Gastrointestinal Microbiome, colon cancer, 030220 oncology & carcinogenesis, Hereditary hemochromatosis, Colonic Neoplasms, Cancer research, medicine.symptom, HFE-null mouse, business, Dysbiosis |
| الوصف: | Hereditary hemochromatosis (HH), an iron-overload disease, is a prevalent genetic disorder. As excess iron causes a multitude of metabolic disturbances, we postulated that iron overload in HH disrupts colonic homeostasis and colon–microbiome interaction and exacerbates the development and progression of colonic inflammation and colon cancer. To test this hypothesis, we examined the progression and severity of colitis and colon cancer in a mouse model of HH (Hfe−/−), and evaluated the potential contributing factors. We found that experimentally induced colitis and colon cancer progressed more robustly in Hfe−/− mice than in wild-type mice. The underlying causes were multifactorial. Hfe−/− colons were leakier with lower proliferation capacity of crypt cells, which impaired wound healing and amplified inflammation-driven tissue injury. The host/microflora axis was also disrupted. Sequencing of fecal 16S RNA revealed profound changes in the colonic microbiome in Hfe−/− mice in favor of the pathogenic bacteria belonging to phyla Proteobacteria and TM7. There was an increased number of bacteria adhered onto the mucosal surface of the colonic epithelium in Hfe−/− mice than in wild-type mice. Furthermore, the expression of innate antimicrobial peptides, the first-line of defense against bacteria, was lower in Hfe−/− mouse colon than in wild-type mouse colon; the release of pro-inflammatory cytokines upon inflammatory stimuli was also greater in Hfe−/− mouse colon than in wild-type mouse colon. These data provide evidence that excess iron accumulation in colonic tissue as happens in HH promotes colitis and colon cancer, accompanied with bacterial dysbiosis and loss of function of the intestinal/colonic barrier. |
| اللغة: | English |
| تدمد: | 1470-8728 0264-6021 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::db83252bbf3a550e0e430f3053888bb7Test http://europepmc.org/articles/PMC7557149Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....db83252bbf3a550e0e430f3053888bb7 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14708728 02646021 |
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