ArticleArchives of toxicology2021
Chronic intestinal inflammation drives colorectal tumor formation triggered by dietary heme iron in vivo.
Article in Archives of toxicology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Dietary inflammatory index and the risk of colorectal adenomas and cancer: a systematic review and dose-response meta-analysis.Nutrition journal · 2025Pooled it
- Blastocyst-Derived Lactic Acid Regulates Uterine Epithelial Receptivity and Stromal Decidualization via the HIF1α-HO-1-Heme Metabolic Axis.Antioxidants (Basel, Switzerland) · 2026Article
- The EduNutriCRC Questionnaire: A Pilot Knowledge-Attitudes-Practices Study on Nutritional Prevention of Colorectal Cancer in Romanian Adults.Nutrients · 2026Article
- Iron Metabolism in the Colorectal Tumor Microenvironment: From Preneoplastic Lesions to Cancer Progression.International journal of molecular sciences · 2026Review
- TGF-β Pathway-Based Polygenic Risk Score Modifies the Association between Red Meat Intake and Colorectal Cancer Risk: Application of a Novel Pathway-Based PRS Method.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2026Article
- Cellular Senescence Triggered by Food and Environmental Genotoxins.International journal of molecular sciences · 2026Review
- Epithelial HO-1 regulates iron availability and promotes colonic tumorigenesis in a context-dependent manner.JCI insight · 2026Article
- Can tissue immune states shape the risk of hyperprogressive disease?Frontiers in immunology · 2026Review
- Review
- Red meat intake interacts with a TGF-β-pathway-based polygenic risk score to impact colorectal cancer risk: Application of a novel approach for polygenic risk score construction.medRxiv : the preprint server for health sciences · 2025Article
- Dietary Manipulation on Gut Microbiome in Patients with Diabetes and Colorectal cancer.Current nutrition reports · 2025Review
- Iron and the Intestinal Microbiome.Advances in experimental medicine and biology · 2025Review
- Progress of research on γδ T cells in colorectal cancer (Review).Oncology reports · 2024Review
- Iron Supplementation Increases Tumor Burden and Alters Protein Expression in a Mouse Model of Human Intestinal Cancer.Nutrients · 2024Article
- Pathological significance of heme oxygenase-1 as a potential tumor promoter in heme-induced colorectal carcinogenesis.Cancer pathogenesis and therapy · 2024Review
- 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
- Redox Homeostasis and Nrf2-Regulated Mechanisms Are Relevant to Male Infertility.Antioxidants (Basel, Switzerland) · 2024Review
- Heme Oxygenase-1 and Its Role in Colorectal Cancer.Antioxidants (Basel, Switzerland) · 2023Review
- Effects of sodium nitrite reduction, removal or replacement on cured and cooked meat for microbiological growth, food safety, colon ecosystem, and colorectal carcinogenesis in Fischer 344 rats.NPJ science of food · 2023Article
- DNA Alkylation Damage by Nitrosamines and Relevant DNA Repair Pathways.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The consumption of red meat is associated with an increased risk for colorectal cancer (CRC). Multiple lines of evidence suggest that heme iron as abundant constituent of red meat is responsible for its carcinogenic potential. However, the underlying mechanisms are not fully understood and particularly the role of intestinal inflammation has not been investigated. To address this important issue, we analyzed the impact of heme iron (0.25 µmol/g diet) on the intestinal microbiota, gut inflammation and colorectal tumor formation in mice. An iron-balanced diet with ferric citrate (0.25 µmol/g diet) was used as reference. 16S rRNA sequencing revealed that dietary heme reduced α-diversity and caused a persistent intestinal dysbiosis, with a continuous increase in gram-negative Proteobacteria. This was linked to chronic gut inflammation and hyperproliferation of the intestinal epithelium as attested by mini-endoscopy, histopathology and immunohistochemistry. Dietary heme triggered the infiltration of myeloid cells into colorectal mucosa with an increased level of COX-2 positive cells. Furthermore, flow cytometry-based phenotyping demonstrated an increased number of T cells and B cells in the lamina propria following heme intake, while γδ-T cells were reduced in the intraepithelial compartment. Dietary heme iron catalyzed formation of fecal N-nitroso compounds and was genotoxic in intestinal epithelial cells, yet suppressed intestinal apoptosis as evidenced by confocal microscopy and western blot analysis. Finally, a chemically induced CRC mouse model showed persistent intestinal dysbiosis, chronic gut inflammation and increased colorectal tumorigenesis following heme iron intake. Altogether, this study unveiled intestinal inflammation as important driver in heme iron-associated colorectal carcinogenesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.