scholarly journals Microbiota and Colorectal Cancer: From Gut to Bedside

2021 ◽  
Vol 12 ◽  
Author(s):  
Miguel Silva ◽  
Valentina Brunner ◽  
Markus Tschurtschenthaler
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiota ◽  
Immune Cell ◽  
Tumour Progression ◽  
Cellular Transformation ◽  
Intestinal Epithelial ◽  
Therapeutic Drugs ◽  
New Findings ◽  
Current Therapies ◽  
Health And Disease

Colorectal cancer (CRC) is a complex condition with heterogeneous aetiology, caused by a combination of various environmental, genetic, and epigenetic factors. The presence of a homeostatic gut microbiota is critical to maintaining host homeostasis and determines the delicate boundary between health and disease. The gut microbiota has been identified as a key environmental player in the pathogenesis of CRC. Perturbations of the gut microbiota structure (loss of equilibrium and homeostasis) are associated with several intestinal diseases including cancer. Such dysbiosis encompasses the loss of beneficial microorganisms, outgrowth of pathogens and pathobionts and a general loss of local microbiota diversity and richness. Notably, several mechanisms have recently been identified how bacteria induce cellular transformation and promote tumour progression. In particular, the formation of biofilms, the production of toxic metabolites or the secretion of genotoxins that lead to DNA damage in intestinal epithelial cells are newly discovered processes by which the microbiota can initiate tumour formation. The gut microbiota has also been implicated in the metabolism of therapeutic drugs (conventional chemotherapy) as well as in the modulation of radiotherapy responses and targeted immunotherapy. These new findings suggest that the efficacy of a given therapy depends on the composition of the host’s gut microbiota and may therefore vary from patient to patient. In this review we discuss the role of host-microbiota interactions in cancer with a focus on CRC pathogenesis. Additionally, we show how gut bacteria can be exploited in current therapies and how mechanisms directed by microbiota, such as immune cell boost, probiotics and oncolytic bacteria, can be applied in the development of novel therapies.

scholarly journals A Crosstalk between Diet, Microbiome and microRNA in Epigenetic Regulation of Colorectal Cancer

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2428
Author(s):  
Małgorzata Guz ◽  
Witold Jeleniewicz ◽  
Anna Malm ◽  
Izabela Korona-Glowniak
Keyword(s):  
Colorectal Cancer ◽  
Gastrointestinal Tract ◽  
Gut Microbiota ◽  
Intestinal Microbiota ◽  
Current Knowledge ◽  
Vital Role ◽  
Disease States ◽  
Health And Disease ◽  
Dietary Components ◽  
Non Coding Rnas

A still growing interest between human nutrition in relation to health and disease states can be observed. Dietary components shape the composition of microbiota colonizing our gastrointestinal tract which play a vital role in maintaining human health. There is a strong evidence that diet, gut microbiota and their metabolites significantly influence our epigenome, particularly through the modulation of microRNAs. These group of small non-coding RNAs maintain cellular homeostasis, however any changes leading to impaired expression of miRNAs contribute to the development of different pathologies, including neoplastic diseases. Imbalance of intestinal microbiota due to diet is primary associated with the development of colorectal cancer as well as other types of cancers. In the present work we summarize current knowledge with particular emphasis on diet-microbiota-miRNAs axis and its relation to the development of colorectal cancer.

scholarly journals The Role of the Gut Microbiome in Colorectal Cancer

2018 ◽  
Vol 31 (03) ◽  
pp. 192-198 ◽  
Author(s):  
Grace Chen
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Microbial Community ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Intestinal Health ◽  
Genotoxic Effects ◽  
Bacterial Populations ◽  
Health And Disease

AbstractThere is increasing evidence that the gut microbiome, which consists of trillions of microbes representing over 1,000 species of bacteria with over 3 million genes, significantly impacts intestinal health and disease. The gut microbiota not only is capable of promoting intestinal homeostasis and antitumor responses but can also contribute to chronic dysregulated inflammation as well as have genotoxic effects that lead to carcinogenesis. Whether the gut microbiota maintains health or promotes colon cancer may ultimately depend on the composition of the gut microbiome and the balance within the microbial community of protective and detrimental bacterial populations. Disturbances in the normal balanced state of a healthful microbiome, known as dysbiosis, have been observed in patients with colorectal cancer (CRC); however, whether these alterations precede and cause CRC remains to be determined. Nonetheless, studies in mice strongly suggest that the gut microbiota can modulate susceptibility to CRC, and therefore may serve as both biomarkers and therapeutic targets.

scholarly journals Abstract 952: Modulation of immune cell trafficking into human colorectal cancer by gut microbiota

2017 ◽  
Author(s):  
Eleonora Cremonesi ◽  
Jesus G. Garzón ◽  
Valeria Governa ◽  
Valentina Mele ◽  
Francesca Amicarella ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiota ◽  
Immune Cell ◽  
Cell Trafficking ◽  
Human Colorectal Cancer ◽  
Immune Cell Trafficking

scholarly journals Host–MicroRNA–Microbiota Interactions in Colorectal Cancer

Genes ◽  
2019 ◽  
Vol 10 (4) ◽  
pp. 270 ◽  
Author(s):  
Ce Yuan ◽  
Clifford J. Steer ◽  
Subbaya Subramanian
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiota ◽  
Tumor Cells ◽  
Immune Cell ◽  
Review Article ◽  
Microbiota Composition ◽  
Cell Fractions ◽  
High Level ◽  
Gut Microbiota Composition

Changes in gut microbiota composition have consistently been observed in patients with colorectal cancer (CRC). Yet, it is not entirely clear how the gut microbiota interacts with tumor cells. We know that tumor cells undergo a drastic change in energy metabolism, mediated by microRNAs (miRNAs), and that tumor-derived miRNAs affect the stromal and immune cell fractions of the tumor microenvironment. Recent studies suggest that host intestinal miRNAs can also affect the growth and composition of the gut microbiota. Our previous CRC studies showed a high-level of interconnectedness between host miRNAs and their microbiota. Considering all the evidence to date, we postulate that the altered nutrient composition and miRNA expression in the CRC microenvironment selectively exerts pressure on the surrounding microbiota, leading to alterations in its composition. In this review article, we present our current understanding of the role of miRNAs in mediating host–microbiota interactions in CRC.

scholarly journals Colitis‐induced colorectal cancer and intestinal epithelial estrogen receptor beta impact gut microbiota diversity

2019 ◽  
Vol 144 (12) ◽  
pp. 3086-3098 ◽  
Author(s):  
Ahmed Ibrahim ◽  
Luisa W. Hugerth ◽  
Linnea Hases ◽  
Ashish Saxena ◽  
Maike Seifert ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Estrogen Receptor ◽  
Gut Microbiota ◽  
Estrogen Receptor Beta ◽  
Intestinal Epithelial ◽  
Microbiota Diversity ◽  
Receptor Beta

The in situ local immune response, tumour senescence, and proliferation in colorectal cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 412-412
Author(s):  
Campbell SD Roxburgh ◽  
Colin H Richards ◽  
Arfon Powell ◽  
Donald C. Mcmillan ◽  
Joanne E. Edwards ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Cell ◽  
Immune Responses ◽  
Cancer Cell ◽  
Cancer Survival ◽  
Immune Cell ◽  
Tumour Progression ◽  
Low Grade ◽  
Cd8 Cells ◽  
Immune Cell Infiltrates

412 Background: Immune cell infiltrates play a key role in determining colorectal cancer outcome. It is unclear whether they are tumour or host specific. Increased immunogenicity may relate to senescence or proliferation. Senescence, a state of cell-cycle arrest, slows tumour progression. In animal models, senescence associated regression is mediated by upregulated antitumour immune responses. High proliferation may provoke immune responses. Relationships between senescence, proliferation and immune cell infiltrates have not previously been studied. We explore whether p16ink4a associated senescence relates to T cell infiltrates in colorectal tumours and whether p16ink4a expression, proliferation and T cell infiltrates confer similar survival relationships. Methods: Immunostaining of nuclear p16inka and Ki67 was performed using a tissue microarray. Nuclear p16inkaand Ki67 were scored as high or low expression. (T cell markers CD3/CD45RO/CD8/FOXP3) were scored high/low grade on corresponding full sections (margin/stroma/ cancer cell nest). Results: 230 Stage I-III cancers were studied. High nuclear p16ink4a was expressed in 63% and high proliferation (Ki67 >15% ) in 61%. P16ink4a expression related to reduced margin, stroma and cancer cell nest (CCN) CD45RO cells (P=0.054, P=0.062, P=0.025) and reduced margin CD8 cells (P=0.016). High Ki67 labeling related to increased margin, and CCN CD3 cells (P=0.017, P<0.001), increased margin and CCN CD45RO cells (P=0.023, P<0.001), increased margin, stroma and CCN FOXP3 cells (P<0.001, P=0.001, P<0.001) and increased margin and CCN CD8 cells (P=0.026, P=0.001). On multivariate analysis, TNM stage (P<0.001), low margin CD3 (P=0.014), low margin CD8 (P=0.037), low proliferation (Ki67) (P=0.013) and low senescence (P16ink4a) (P=0.002) conferred poorer cancer survival. Conclusions: p16ink4a expression, proliferation and immune cell infiltrates are independent prognostic factors in colorectal cancer. Proliferation relates to increasing T cell infiltrates but independently influences survival. P16ink4a associated senescence does not appear to mediate improved outcome by upregulating T cell responses. Relationships observed here suggest the opposite.

Abstract A123: Modulation of immune cell trafficking into human colorectal cancer by gut microbiota

2016 ◽  
Author(s):  
Eleonora Cremonesi ◽  
Francesca Amicarella ◽  
Jesus Francisco Glaus Garzon ◽  
Valeria Governa ◽  
Manuele Giuseppe Muraro ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiota ◽  
Immune Cell ◽  
Cell Trafficking ◽  
Human Colorectal Cancer ◽  
Immune Cell Trafficking

scholarly journals Contribution of Gut Bacteria to Liver Pathobiology

2010 ◽  
Vol 2010 ◽  
pp. 1-13 ◽  
Author(s):  
Gakuhei Son ◽  
Michael Kremer ◽  
Ian N. Hines
Keyword(s):  
Gut Microbiota ◽  
Immune Cell ◽  
Tissue Injury ◽  
Gut Bacteria ◽  
First Line ◽  
Ischemic Tissue ◽  
Toxin Exposure ◽  
Broad Array ◽  
Health And Disease ◽  
The Relationship

Emerging evidence suggests a strong interaction between the gut microbiota and health and disease. The interactions of the gut microbiota and the liver have only recently been investigated in detail. Receiving approximately 70% of its blood supply from the intestinal venous outflow, the liver represents the first line of defense against gut-derived antigens and is equipped with a broad array of immune cells (i.e., macrophages, lymphocytes, natural killer cells, and dendritic cells) to accomplish this function. In the setting of tissue injury, whereby the liver is otherwise damaged (e.g., viral infection, toxin exposure, ischemic tissue damage, etc.), these same immune cell populations and their interactions with the infiltrating gut bacteria likely contribute to and promote these pathologies. The following paper will highlight recent studies investigating the relationship between the gut microbiota, liver biology, and pathobiology. Defining these connections will likely provide new targets for therapy or prevention of a wide variety of acute and chronic liver pathologies.

scholarly journals Antibiotic-induced disturbances of the gut microbiota result in accelerated breast tumour growth via a mast cell-dependent pathway

2020 ◽  
Author(s):  
Benjamin M. Kirkup ◽  
Alastair M. McKee ◽  
Matthew Madgwick ◽  
Christopher A Price ◽  
Sally A Dreger ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mast Cell ◽  
Mast Cells ◽  
Gut Microbiota ◽  
Cancer Progression ◽  
Tumour Growth ◽  
Immune Cell ◽  
Tumour Progression ◽  
Primary Tumour ◽  
The Body

AbstractThe diverse community of commensal microbes that comprise the gut microbiota is known to play an integral role in human health, not least through its ability to regulate host immune responses and metabolic pathways. Alterations to the homeostasis of this community, including through the use of broad-spectrum antibiotics, have already been associated with the progression of several cancers, namely melanoma and liver. The aggressive nature of breast cancer (BrCa), largely due to its ability to metastasize early, has ranked the disease with the second highest mortality rate of all cancers globally. Yet the body of research into the complex relationship between the microbiota and BrCa is still limited. This study found that a depletion of the microbiota, through the administration of antibiotics, significantly increased the rate of primary tumour progression in mouse BrCa models. We show that antibiotic-induced microbiota disturbances lead to changes in behaviour of a relatively obscure tumour-immune cell population: mast cells. We observed increases in tumour stroma-associated mast cells in antibiotic treated animals. Moreover, inhibition of mast cell degranulation, via cromolyn, slowed tumour progression in antibiotic treated animals but not in control animals. Thus, it appears that a perturbed microbiota drives stroma-associated mast cell recruitment and activation, which in turn promotes primary tumour growth through an as yet unknown mechanism.One Sentence Summary: We show that breast cancer progression is accelerated through a unique/novel immune response involving mast cells as a result of an antibiotic induced perturbation of the gut microbiota in a mouse model.

Gut Microbiota in Health and Disease

2010 ◽  
Vol 90 (3) ◽  
pp. 859-904 ◽  
Author(s):  
Inna Sekirov ◽  
Shannon L. Russell ◽  
L. Caetano M. Antunes ◽  
B. Brett Finlay
Keyword(s):  
Microbial Community ◽  
Gut Microbiota ◽  
Central Position ◽  
Intestinal Epithelial ◽  
Modeling And Analysis ◽  
Organ Systems ◽  
Key Species ◽  
Health And Disease ◽  
And Function ◽  
Gut Microbial Community

Gut microbiota is an assortment of microorganisms inhabiting the length and width of the mammalian gastrointestinal tract. The composition of this microbial community is host specific, evolving throughout an individual's lifetime and susceptible to both exogenous and endogenous modifications. Recent renewed interest in the structure and function of this “organ” has illuminated its central position in health and disease. The microbiota is intimately involved in numerous aspects of normal host physiology, from nutritional status to behavior and stress response. Additionally, they can be a central or a contributing cause of many diseases, affecting both near and far organ systems. The overall balance in the composition of the gut microbial community, as well as the presence or absence of key species capable of effecting specific responses, is important in ensuring homeostasis or lack thereof at the intestinal mucosa and beyond. The mechanisms through which microbiota exerts its beneficial or detrimental influences remain largely undefined, but include elaboration of signaling molecules and recognition of bacterial epitopes by both intestinal epithelial and mucosal immune cells. The advances in modeling and analysis of gut microbiota will further our knowledge of their role in health and disease, allowing customization of existing and future therapeutic and prophylactic modalities.

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