ArticleThe Biochemical journal2020
Hereditary hemochromatosis promotes colitis and colon cancer and causes bacterial dysbiosis in mice.
Article in The Biochemical journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Gut microbiota bridges dietary nutrients and host immunity.Science China. Life sciences · 2023Pooled it
- The gut microbiota metabolite trimethylamine-N-oxide in children with β-thalassemia: potential implication for iron-induced renal tubular dysfunction.Pediatric research · 2025Article
- Iron at the crossroads of host-microbiome interactions in health and disease.Nature microbiology · 2025Review
- Inflammatory bowel disease and hereditary hemochromatosis: A case series.JPGN reports · 2025Article
- An overview of the current evidences on the role of iron in colorectal cancer: a review.Frontiers in oncology · 2025Review
- Inhibition of IRP2-dependent reprogramming of iron metabolism suppresses tumor growth in colorectal cancer.Cell communication and signaling : CCS · 2024Article
- Article
- Genome-Wide Gene-Environment Interaction Analyses to Understand the Relationship between Red Meat and Processed Meat Intake and Colorectal Cancer Risk.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2024Article
- Colonic ketogenesis, a microbiota-regulated process, contributes to blood ketones and protects against colitis in mice.The Biochemical journal · 2024Article
- Sigma Receptors: Novel Regulators of Iron/Heme Homeostasis and Ferroptosis.International journal of molecular sciences · 2023Review
- Role of ferroptosis in the pathogenesis and as a therapeutic target of inflammatory bowel disease (Review).International journal of molecular medicine · 2023Review
- Polycystic ovary syndrome and iron overload: biochemical link and underlying mechanisms with potential novel therapeutic avenues.Bioscience reports · 2023Article
- Effect of Diets Varying in Iron and Saturated Fat on the Gut Microbiota and Intestinal Inflammation: A Crossover Feeding Study among Older Females with Obesity.Nutrition and cancer · 2023Article
- The role of iron in host-microbiota crosstalk and its effects on systemic glucose metabolism.Nature reviews. Endocrinology · 2022Review
- Binding of Citrate-FeInternational journal of molecular sciences · 2022Article
- Inhibiting Ferroptosis: A Novel Approach for Ulcerative Colitis Therapeutics.Oxidative medicine and cellular longevity · 2022Review
- Atractylenolide I inhibits antibiotic-induced dysbiosis of the intestinal microbiome.Annals of translational medicine · 2021Article
- Iron Reshapes the Gut Microbiome and Host Metabolism.Journal of lipid and atherosclerosis · 2021Review
- Consequences of NaCT/SLC13A5/mINDY deficiency: good versus evil, separated only by the blood-brain barrier.The Biochemical journal · 2021Review
- Emerging Pathological Engagement of Ferroptosis in Gut Diseases.Oxidative medicine and cellular longevity · 2021Review
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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