Influence of Iron on the Gut Microbiota in Colorectal Cancer

Perturbations of the colonic microbiota can contribute to the initiation and progression of colorectal cancer, leading to an increase in pathogenic bacteria at the expense of protective bacteria. This can contribute to disease through increasing carcinogenic metabolite/toxin production, inducing inflammation, and activating oncogenic signaling. To limit disease progression, external factors that may influence the colonic microbiota need to be considered in patients with colorectal cancer. One major factor that can influence the colonic microbiota is iron. Iron is an essential micronutrient that is required by both prokaryotes and eukaryotes for cellular function. Most pathogenic bacteria have heightened iron acquisition mechanisms and therefore tend to outcompete protective bacteria for free iron. Colorectal cancer patients often present with anemia due to iron deficiency, and thus they require iron therapy. Depending upon the route of administration, iron therapy has the potential to contribute to a procarciongenic microbiota. Orally administered iron is the common treatment for anemia in these patients but can lead to an increased gut iron concentration. This suggests the need to reassess the route of iron therapy in these patients. Currently, this has only been assessed in murine studies, with human trials being necessary to unravel the potential microbial outcomes of iron therapy.

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Short-term effect of preoperative intravenous iron therapy in colorectal cancer patients with anemia: results of a cohort study

Transfusion ◽

10.1111/trf.14456 ◽

2017 ◽

Vol 58 (3) ◽

pp. 795-803 ◽

Cited By ~ 12

Author(s):

Michael Jordi Wilson ◽

Jan Willem Dekker ◽

Emma Bruns ◽

Wernard Borstlap ◽

Johannes Jeekel ◽

...

Keyword(s):

Colorectal Cancer ◽

Cohort Study ◽

Cancer Patients ◽

Intravenous Iron ◽

Term Effect ◽

Iron Therapy ◽

Short Term ◽

Short Term Effect ◽

Intravenous Iron Therapy ◽

Colorectal Cancer Patients

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Su1995 MICROBIOLOGICAL AND IMMUNOLOGICAL INFLAMMATORY IMMUNE RESPONSES IN ANAEMIC COLORECTAL CANCER PATIENTS TREATED WITH ORAL IRON THERAPY

Gastroenterology ◽

10.1016/s0016-5085(20)32521-x ◽

2020 ◽

Vol 158 (6) ◽

pp. S-738

Author(s):

Oliver Phipps ◽

Mohammed Nabil Quraishi ◽

Aditi Kumar ◽

Edward Dickson ◽

Oliver Ng ◽

...

Keyword(s):

Colorectal Cancer ◽

Immune Responses ◽

Cancer Patients ◽

Oral Iron ◽

Iron Therapy ◽

Oral Iron Therapy ◽

Colorectal Cancer Patients

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Su1994 ORAL IRON THERAPY PROMOTES A PROINFLAMMATORY GUT MICROBIOTA IN COLORECTAL CANCER PATIENTS WITH IRON DEFICIENCY ANAEMIA

Gastroenterology ◽

10.1016/s0016-5085(20)32520-8 ◽

2020 ◽

Vol 158 (6) ◽

pp. S-737-S-738

Author(s):

Oliver Phipps ◽

Mohammed Nabil Quraishi ◽

Aditi Kumar ◽

Edward Dickson ◽

Oliver Ng ◽

...

Keyword(s):

Colorectal Cancer ◽

Iron Deficiency ◽

Gut Microbiota ◽

Cancer Patients ◽

Iron Deficiency Anaemia ◽

Oral Iron ◽

Iron Therapy ◽

Deficiency Anaemia ◽

Oral Iron Therapy ◽

Colorectal Cancer Patients

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Analysis of changes in microbiome compositions related to the prognosis of colorectal cancer patients based on tissue-derived 16S rRNA sequences

Journal of Translational Medicine ◽

10.1186/s12967-021-03154-0 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Sukjung Choi ◽

Jongsuk Chung ◽

Mi-La Cho ◽

Donghyun Park ◽

Sun Shim Choi

Keyword(s):

Colorectal Cancer ◽

16S Rrna ◽

Pathogenic Bacteria ◽

Fusobacterium Nucleatum ◽

Amplicon Sequencing ◽

Normal Tissues ◽

16S Rrna Amplicon Sequencing ◽

Tumor Tissues ◽

Colorectal Cancer Patients ◽

Host Genes

Abstract Background Comparing the microbiome compositions obtained under different physiological conditions has frequently been attempted in recent years to understand the functional influence of microbiomes in the occurrence of various human diseases. Methods In the present work, we analyzed 102 microbiome datasets containing tumor- and normal tissue-derived microbiomes obtained from a total of 51 Korean colorectal cancer (CRC) patients using 16S rRNA amplicon sequencing. Two types of comparisons were used: ‘normal versus (vs.) tumor’ comparison and ‘recurrent vs. nonrecurrent’ comparison, for which the prognosis of patients was retrospectively determined. Results As a result, we observed that in the ‘normal vs. tumor’ comparison, three phyla, Firmicutes, Actinobacteria, and Bacteroidetes, were more abundant in normal tissues, whereas some pathogenic bacteria, including Fusobacterium nucleatum and Bacteroides fragilis, were more abundant in tumor tissues. We also found that bacteria with metabolic pathways related to the production of bacterial motility proteins or bile acid secretion were more enriched in tumor tissues. In addition, the amount of these two pathogenic bacteria was positively correlated with the expression levels of host genes involved in the cell cycle and cell proliferation, confirming the association of microbiomes with tumorigenic pathway genes in the host. Surprisingly, in the ‘recurrent vs. nonrecurrent’ comparison, we observed that these two pathogenic bacteria were more abundant in the patients without recurrence than in the patients with recurrence. The same conclusion was drawn in the analysis of both normal and tumor-derived microbiomes. Conclusions Taken together, it seems that understanding the composition of tissue microbiomes is useful for predicting the prognosis of CRC patients.

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Biomarkers Discovery for Colorectal Cancer: A Review on Tumor Endothelial Markers as Perspective Candidates

Disease Markers ◽

10.1155/2016/4912405 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 9

Author(s):

Łukasz Pietrzyk

Keyword(s):

Colorectal Cancer ◽

Early Detection ◽

Fundamental Problem ◽

Successful Outcome ◽

Clinical Approach ◽

Oncogenic Signaling ◽

Endothelial Markers ◽

Common Cancer ◽

Noninvasive Biomarkers ◽

Colorectal Cancer Patients

Colorectal cancer (CRC) is the third most common cancer in the world. The early detection of CRC, during the promotion/progression stages, is an enormous challenge for a successful outcome and remains a fundamental problem in clinical approach. Despite the continuous advancement in diagnostic and therapeutic methods, there is a need for discovery of sensitive and specific, noninvasive biomarkers. Tumor endothelial markers (TEMs) are associated with tumor-specific angiogenesis and are potentially useful to discriminate between tumor and normal endothelium. The most promising TEMs for oncogenic signaling in CRC appeared to be the TEM1, TEM5, TEM7, and TEM8. Overexpression of TEMs especially TEM1, TEM7, and TEM8 in colorectal tumor tissue compared to healthy tissue suggests their role in tumor blood vessels formation. Thus TEMs appear to be perspective candidates for early detection, monitoring, and treatment of CRC patients. This review provides an update on recent data on tumor endothelial markers and their possible use as biomarkers for screening, diagnosis, and therapy of colorectal cancer patients.

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The effect of intravenous iron therapy on long-term survival in anaemic colorectal cancer patients: Results from a matched cohort study

Surgical Oncology ◽

10.1016/j.suronc.2018.03.005 ◽

2018 ◽

Vol 27 (2) ◽

pp. 192-199 ◽

Cited By ~ 3

Author(s):

M.J. Wilson ◽

J.W.T. Dekker ◽

S. Buettner ◽

J.J. Harlaar ◽

J. Jeekel ◽

...

Keyword(s):

Colorectal Cancer ◽

Cohort Study ◽

Cancer Patients ◽

Intravenous Iron ◽

Iron Therapy ◽

Matched Cohort ◽

Term Survival ◽

Intravenous Iron Therapy ◽

Colorectal Cancer Patients

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Colorectal cancer treatment using bacteria: focus on molecular mechanisms

BMC Microbiology ◽

10.1186/s12866-021-02274-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Sara Ebrahimzadeh ◽

Hossein Ahangari ◽

Alireza Soleimanian ◽

Kamran Hosseini ◽

Vida Ebrahimi ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Therapy ◽

Cancer Treatment ◽

Pathogenic Bacteria ◽

Molecular Mechanisms ◽

Treatment Strategies ◽

Cancer Etiology ◽

Beneficial Effects ◽

Life Threatening ◽

Colorectal Cancer Patients

Abstract Background Colorectal cancer which is related to genetic and environmental risk factors, is among the most prevalent life-threatening cancers. Although several pathogenic bacteria are associated with colorectal cancer etiology, some others are considered as highly selective therapeutic agents in colorectal cancer. Nowadays, researchers are concentrating on bacteriotherapy as a novel effective therapeutic method with fewer or no side effects to pay the way of cancer therapy. The introduction of advanced and successful strategies in bacterial colorectal cancer therapy could be useful to identify new promising treatment strategies for colorectal cancer patients. Main text In this article, we scrutinized the beneficial effects of bacterial therapy in colorectal cancer amelioration focusing on different strategies to use a complete bacterial cell or bacterial-related biotherapeutics including toxins, bacteriocins, and other bacterial peptides and proteins. In addition, the utilization of bacteria as carriers for gene delivery or other known active ingredients in colorectal cancer therapy are reviewed and ultimately, the molecular mechanisms targeted by the bacterial treatment in the colorectal cancer tumors are detailed. Conclusions Application of the bacterial instrument in cancer treatment is on its way through becoming a promising method of colorectal cancer targeted therapy with numerous successful studies and may someday be a practical strategy for cancer treatment, particularly colorectal cancer.

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Different hotspot p53 mutants exert distinct phenotypes and predict outcome of colorectal cancer patients

10.21203/rs.3.rs-523301/v1 ◽

2021 ◽

Author(s):

Ori Hassin ◽

Nishanth Belugali Nataraj ◽

Michal Shreberk-Shaked ◽

Yael Aylon ◽

Rona Yaeger ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Progression ◽

Regulatory Elements ◽

Migration And Invasion ◽

Missense Mutations ◽

Oncogenic Signaling ◽

Transcriptional Signature ◽

Colorectal Cancer Patients

Abstract Colorectal cancer (CRC) is the third most common cancer worldwide. The TP53 gene is mutated in approximately 60% of all CRC cases. Sporadic CRC is characterized by high prevalence of TP53 hotspot missense mutations. In particular, over 20 percent of all TP53-mutated CRC tumors carry either the p53R175H structural mutant or the p53R273H DNA contact mutant. Importantly, clinical data analysis suggests that CRC tumors harboring p53 R273 mutations are more prone to progress to metastatic disease than those with R175 mutations, in association with decreased survival. By combining in vitro CRC cell line models and human CRC data mining, we identified a unique transcriptional signature orchestrated by p53R273H, implicating activation of oncogenic signaling pathways and predicting worse patient outcome. Concordantly, p53R273H selectively promotes rapid CRC cell spreading, migration and invasion in vitro and metastasis in vivo. Mechanistically, the transcriptional output of p53R273H is associated with, and presumably driven by, its preferential binding to regulatory elements of R273 signature genes. Together, this demonstrates that different TP53 missense mutations contribute differently to cancer progression, and that p53R273H possesses distinct gain-of-function activities in CRC that bear on disease course and possibly on patient management strategy. Given that practically all current analytical cancer gene panels include TP53, elucidation of the differential impact of distinct TP53 mutations on disease features is expected to make information on TP53 mutations more actionable and holds potential for better precision-based medicine.

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