The gastrointestinal microbiota and colorectal cancer

The human gut is home to a complex and diverse microbiota that contributes to the overall homeostasis of the host. Increasingly, the intestinal microbiota is recognized as an important player in human illness such as colorectal cancer (CRC), inflammatory bowel diseases, and obesity. CRC in itself is one of the major causes of cancer mortality in the Western world. The mechanisms by which bacteria contribute to CRC are complex and not fully understood, but increasing evidence suggests a link between the intestinal microbiota and CRC as well as diet and inflammation, which are believed to play a role in carcinogenesis. It is thought that the gut microbiota interact with dietary factors to promote chronic inflammation and CRC through direct influence on host cell physiology, cellular homeostasis, energy regulation, and/or metabolism of xenobiotics. This review provides an overview on the role of commensal gut microbiota in the development of human CRC and explores its association with diet and inflammation.

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

Nutrients ◽

10.3390/nu13072428 ◽

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.

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The intestinal microbiota, gastrointestinal environment and colorectal cancer: a putative role for probiotics in prevention of colorectal cancer?

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00110.2011 ◽

2011 ◽

Vol 301 (3) ◽

pp. G401-G424 ◽

Cited By ~ 125

Author(s):

M. Andrea Azcárate-Peril ◽

Michael Sikes ◽

José M. Bruno-Bárcena

Keyword(s):

Colorectal Cancer ◽

Intestinal Microbiota ◽

Defense Mechanisms ◽

High Throughput Sequencing ◽

Safety Evaluation ◽

Health Benefit ◽

The United States ◽

Dietary Factors ◽

Colorectal Adenomas ◽

Food Allergies

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the United States, and, even though 5–15% of the total CRC cases can be attributed to individual genetic predisposition, environmental factors could be considered major factors in susceptibility to CRC. Lifestyle factors increasing the risks of CRC include elevated body mass index, obesity, and reduced physical activity. Additionally, a number of dietary elements have been associated with higher or lower incidence of CRC. In this context, it has been suggested that diets high in fruit and low in meat might have a protective effect, reducing the incidence of colorectal adenomas by modulating the composition of the normal nonpathogenic commensal microbiota. In addition, it has been demonstrated that changes in abundance of taxonomic groups have a profound impact on the gastrointestinal physiology, and an increasing number of studies are proposing that the microbiota mediates the generation of dietary factors triggering colon cancer. High-throughput sequencing and molecular taxonomic technologies are rapidly filling the knowledge gaps left by conventional microbiology techniques to obtain a comprehensive catalog of the human intestinal microbiota and their associated metabolic repertoire. The information provided by these studies will be essential to identify agents capable of modulating the massive amount of gut bacteria in safe noninvasive manners to prevent CRC. Probiotics, defined as “live microorganisms which, when administered in adequate amounts, confer a health benefit on the host” ( 219 ), are capable of transient modulation of the microbiota, and their beneficial effects include reinforcement of the natural defense mechanisms and protection against gastrointestinal disorders. Probiotics have been successfully used to manage infant diarrhea, food allergies, and inflammatory bowel disease; hence, the purpose of this review was to examine probiotic metabolic activities that may have an effect on the prevention of CRC by scavenging toxic compounds or preventing their generation in situ. Additionally, a brief consideration is given to safety evaluation and production methods in the context of probiotics efficacy.

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Probiotics, Prebiotics, and Synbiotics: Gut and Beyond

Gastroenterology Research and Practice ◽

10.1155/2012/872716 ◽

2012 ◽

Vol 2012 ◽

pp. 1-16 ◽

Cited By ~ 72

Author(s):

Usha Vyas ◽

Natarajan Ranganathan

Keyword(s):

Gut Microbiota ◽

Intestinal Microbiota ◽

Intestinal Tract ◽

Gastric Ulcers ◽

Colon Cancers ◽

Bowel Diseases ◽

Health And Disease ◽

The Individual ◽

And Control ◽

Human Intestinal Tract

The human intestinal tract has been colonized by thousands of species of bacteria during the coevolution of man and microbes. Gut-borne microbes outnumber the total number of body tissue cells by a factor of ten. Recent metagenomic analysis of the human gut microbiota has revealed the presence of some 3.3 million genes, as compared to the mere 23 thousand genes present in the cells of the tissues in the entire human body. Evidence for various beneficial roles of the intestinal microbiota in human health and disease is expanding rapidly. Perturbation of the intestinal microbiota may lead to chronic diseases such as autoimmune diseases, colon cancers, gastric ulcers, cardiovascular disease, functional bowel diseases, and obesity. Restoration of the gut microbiota may be difficult to accomplish, but the use of probiotics has led to promising results in a large number of well-designed (clinical) studies. Microbiomics has spurred a dramatic increase in scientific, industrial, and public interest in probiotics and prebiotics as possible agents for gut microbiota management and control. Genomics and bioinformatics tools may allow us to establish mechanistic relationships among gut microbiota, health status, and the effects of drugs in the individual. This will hopefully provide perspectives for personalized gut microbiota management.

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The Association between Gut Microbiota and Intestinal Toll-like Receptors Genes Expression in Adenomatous and Colorectal Cancerous patients

10.21203/rs.2.23741/v1 ◽

2020 ◽

Author(s):

Sama Rezasoltani ◽

Maryam Sharafkhah ◽

Hamid Asadzadeh Aghdaei ◽

Meysam Olfatifar ◽

Ehsan Nazemalhosseini Mojarad ◽

...

Keyword(s):

Colorectal Cancer ◽

Gut Microbiota ◽

Intestinal Microbiota ◽

Intestinal Inflammation ◽

Inflammatory Responses ◽

Bacteroides Fragilis ◽

Normal Group ◽

Adenomatous Polyposis ◽

Toll Like Receptors ◽

Genes Expression

Abstract Background: Toll-like receptor (TLR) signaling has been implicated in colorectal cancer (CRC) development. Intestinal microbiota can affect the expression of TLRs, which may induce inflammatory responses and impair the gut homeostasis. Here, we aimed to evaluate certain intestinal microbiota related to TLRs expression in colonic tissues of adenomatous polyposis and CRC patients. Results: Fecal and colonic tissue samples were collected from normal controls (NC), adenomatous (AP) cases and (CRC) patients via colonoscopy for CRC screening during 2016 to 2018. Fecal samples were collected to analyze intestinal bacteria including Streptococcus bovis , Enterococcus faecalis , Bacteroides fragilis , enterotoxigenic Bacteroides fragilis (ETBF) , Fusobacterium nucleatum , Porphyromonas gingivalis, Porphyromonas spp . and Roseburia spp . by real-time PCR. Gene expression of TLR2, TLR4 and TLR5 was examined in colonic tissues by qRT-PCR. Different abundant of gut bacteria were achieved in NC, AP and CRC groups. The genes expression of TLR2, TLR4 and TLR5 were significantly different in AP and CRC cases vs. normal group (P value <0.05). There was a significant relationship between TLR2, TLR4, TLR5 genes expression and Roseburia spp., P. gingivalis and ETBF quantity in normal group. Also significant association between TLR2, TLR4 genes expression levels and the quantity of S.bovis , ETBF, Roseburia spp. and E. faecalis in AP and CRC cases were achieved. Conclusion : Intestinal expression of TLR2, TLR4 and TLR5 is dynamic and depends on gut microbiota. Hence, altered immune activation in response to dysbiotic microbiota may promote intestinal inflammation in a group of patients with AP and CRC. Keyword: Adenomatous polyposis; colorectal cancer; gut microbiota; Toll-like receptors; intestinal inflammation

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Omega-3 PUFAs and gut microbiota: A preventive approach for colorectal cancer

Journal of Biological Research - Bollettino della Società Italiana di Biologia Sperimentale ◽

10.4081/jbr.2021.9954 ◽

2021 ◽

Author(s):

Marco Giammanco ◽

Margherita Mazzola ◽

Manfredi Marco Giammanco ◽

Giovanni Tomasello ◽

Francesco Carini

Keyword(s):

Colorectal Cancer ◽

Fatty Acids ◽

Inflammatory Response ◽

Gut Microbiota ◽

Intestinal Microbiota ◽

Intestinal Bacteria ◽

Omega 3 ◽

Bacterial Composition ◽

Proinflammatory Mediators ◽

Strategic Approach

The influence of diet on the composition of the intestinal microbiota and related pathologies has been known for some time. Some classes of nutrients, such as fatty acids belonging to the omega 3 series, have particular effects on the bacteria that make up the intestinal microbiota. ω-3 PUFAs affect the gut microbiota in three different ways: by modulating the type and abundance of intestinal bacteria, by regulate SCFAs levels, and by alter the levels of proinflammatory mediators. Through these modalities, ω-3 PUFAs could be useful for the prevention of intestinal diseases such as colorectal cancer (CRC). The ability of ω-3 PUFAs to modulate the intestinal inflammatory response, to preserve the integrity of the intestinal mucosa and to modulate the bacterial composition of the intestine, could be useful as a preventive strategic approach to hinder the development of CRC.

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A Link between Chronic Kidney Disease and Gut Microbiota in Immunological and Nutritional Aspects

Nutrients ◽

10.3390/nu13103637 ◽

2021 ◽

Vol 13 (10) ◽

pp. 3637

Author(s):

Paulina Mertowska ◽

Sebastian Mertowski ◽

Julia Wojnicka ◽

Izabela Korona-Głowniak ◽

Ewelina Grywalska ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Immune System ◽

Kidney Disease ◽

Gut Microbiota ◽

Intestinal Microbiota ◽

Kidney Diseases ◽

Disease Onset ◽

Kidney Injury ◽

Dietary Factors

Chronic kidney disease (CKD) is generally progressive and irreversible, structural or functional renal impairment for 3 or more months affecting multiple metabolic pathways. Recently, the composition, dynamics, and stability of a patient’s microbiota has been noted to play a significant role during disease onset or progression. Increasing urea concentration during CKD can lead to an acceleration of the process of kidney injury leading to alterations in the intestinal microbiota that can increase the production of gut-derived toxins and alter the intestinal epithelial barrier. A detailed analysis of the relationship between the role of intestinal microbiota and the development of inflammation within the symbiotic and dysbiotic intestinal microbiota showed significant changes in kidney dysfunction. Several recent studies have determined that dietary factors can significantly influence the activation of immune cells and their mediators. Moreover, dietary changes can profoundly affect the balance of gut microbiota. The aim of this review is to present the importance and factors influencing the differentiation of the human microbiota in the progression of kidney diseases, such as CKD, IgA nephropathy, idiopatic nephropathy, and diabetic kidney disease, with particular emphasis on the role of the immune system. Moreover, the effects of nutrients, bioactive compounds on the immune system in development of chronic kidney disease were reviewed.

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Role of intestinal microbiota in colorectal carcinogenesis (review)

Koloproktologia ◽

10.33878/2073-7556-2021-20-1-68-76 ◽

2021 ◽

Vol 20 (1) ◽

pp. 68-76

Author(s):

M. A. Sukhina ◽

I. A. Lyagina ◽

A. L. Safin ◽

S. A. Frolov ◽

V. N. Kashnikov

Keyword(s):

Colorectal Cancer ◽

Cancer Screening ◽

Gut Microbiota ◽

Intestinal Microbiota ◽

Colorectal Carcinogenesis ◽

Pathogenic Microorganisms ◽

Microbiota Composition ◽

Qualitative And Quantitative ◽

Leading Role

The aim of the review is to show possible links between intestinal microbiota and colorectal carcinogenesis, to describe the procarcinogenic properties of microorganisms associated with the development or proliferation of colorectal cancer. The gut microbiota plays a leading role in metabolism, providing important metabolites to the macroorganism. In humans, there is a spatial variability in the qualitative and quantitative microbiota composition. The intestinal microbiota provides the colony resistance, protecting it from colonization by opportunistic and pathogenic microorganisms. There is more and more data on the role of the gut microbiota in the development of colorectal cancer. The profound study of the gut microbiome in various populations is required, which will allow to identify other microorganisms associated with the development or proliferation of colorectal cancer. It can be used as biomarkers for colorectal cancer screening and predicting the response to immunotherapy.

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Does Subclinical Malabsorption of Carbohydrates Prevent Colorectal Cancer? A Hypothesis

Canadian Journal of Gastroenterology ◽

10.1155/2008/275903 ◽

2008 ◽

Vol 22 (7) ◽

pp. 627-630 ◽

Cited By ~ 1

Author(s):

Terry Dorcen Bolin

Keyword(s):

Colorectal Cancer ◽

Cell Damage ◽

Bacterial Overgrowth ◽

Developed Countries ◽

Dietary Factors ◽

Gdp Per Capita ◽

Western World ◽

Mucosal Cell ◽

Increased Risk ◽

Per Capita

The incidence of colorectal cancer (CRC) is high in the western world and low in Asia and Africa. Fibre and starch are thought to be important protective factors, with a strong inverse relationship between starch consumption and CRC incidence. Whether this is true in Asia, particularly, and Africa is debatable. Because rice is the most easily absorbed of carbohydrates, a mechanism whereby there is an increased starch load in the colon in the Asian population needs to be identified. One possible cause is subclinical malabsorption. This is linked to increased mucosal permeability and low gross domestic product (GDP) per capita, which reflects poor sanitation and water supplies with increased risk for small bowel bacterial overgrowth leading to mucosal cell damage. A potential cause of the dramatic rise in CRC incidence in Japan may relate to its equally dramatic increase in GDP per capita of 600% over 50 years. This correlation appears to be stronger than with other dietary factors including fruit, vegetables and meat. Worldwide, a close correlation exists among low GDP per capita, low CRC incidence and presumed subclinical malabsorption. All these factors combine to maintain a low incidence of CRC in poorly developed countries.

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Role of Intestinal Microbiota on Gut Homeostasis and Rheumatoid Arthritis

Journal of Immunology Research ◽

10.1155/2021/8167283 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Mingxin Li ◽

Fang Wang

Keyword(s):

Rheumatoid Arthritis ◽

Immune System ◽

Gut Microbiota ◽

Intestinal Microbiota ◽

Chronic Inflammatory Disease ◽

Host Immune System ◽

Healthy Controls ◽

Gastrointestinal Microbiota ◽

Intestinal Dysbiosis ◽

Immune Mediated

Rheumatoid arthritis (RA) is a chronic inflammatory disease that is immune mediated. Patients typically present with synovial inflammation, which gradually deteriorates to investigate severe cartilage and bone damage, affecting an individual’s ability to perform basic tasks and impairing the quality of life. When evaluated against healthy controls, patients with RA have notable variations within the constituents of the gut microbiota. The human gastrointestinal tract mucosa is colonized by trillions of commensal microbacteria, which are key actors in the initiation, upkeep, and operation of the host immune system. Gut microbiota dysbiosis can adversely influence the immune system both locally and throughout the host, thus predisposing the host to a number of pathologies, including RA. Proximal intestinal immunomodulatory cells, situated in specific locales within the intestine, are a promising intermediary through which the gastrointestinal microbiota can influence the pathogenesis and progression of RA. In the early stages of the disease, the microbiota appear to differ from those present in healthy controls. This difference may reflect potential autoimmune mechanisms. Research studies evaluating intestinal microbiota have demonstrated that RA is associated with a bacterial population growth or with a decline when judged against control groups. The aim of this review is to examine the studies that connect intestinal dysbiosis with the autoimmune pathways implicated in the pathogenesis of RA.

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Intestinal Microbiota Influences DNA Methylome and Susceptibility to Colorectal Cancer

Genes ◽

10.3390/genes11070808 ◽

2020 ◽

Vol 11 (7) ◽

pp. 808

Author(s):

Aïcha Zouggar ◽

Joshua R. Haebe ◽

Yannick D. Benoit

Keyword(s):

Colorectal Cancer ◽

Inflammatory Bowel Disease ◽

Inflammatory Response ◽

Gut Microbiota ◽

Intestinal Microbiota ◽

Bowel Disease ◽

Colorectal Tumorigenesis ◽

Epigenetic Programming ◽

Inflammatory Bowel ◽

The Impact

In a recent publication, Ansari et al. identified gut microbiota as a critical mediator of the intestinal inflammatory response through epigenetic programming of host intestinal epithelium. Exposure to the microbiota induces Ten-Eleven-Translocation (TET)-dependent hypomethylation of genomic elements regulating genes associated with inflammatory response and colorectal cancer. Here, we discuss the impact of such a discovery on the understanding of how the intestinal microbiota may contribute to epigenetic reprogramming and influence the onset of colorectal tumorigenesis. Finally, we examine the prospect of TET inhibition strategies as a therapeutic and/or preventive approach for colorectal cancer in patients afflicted by inflammatory bowel disease.

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