scholarly journals Manipulation of the Gut Microbiota Reveals Role in Colon Tumorigenesis

mSphere ◽  
2015 ◽  
Vol 1 (1) ◽  
Author(s):  
Joseph P. Zackular ◽  
Nielson T. Baxter ◽  
Grace Y. Chen ◽  
Patrick D. Schloss
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Gut Microbiota ◽  
Murine Model ◽  
Initial Composition ◽  
Bacterial Populations ◽  
Colon Tumorigenesis ◽  
Antibiotic Perturbations ◽  
Proof Of Principle ◽  
Final Proof

ABSTRACT Mounting evidence indicates that alterations to the gut microbiota, the complex community of bacteria that inhabits the gastrointestinal tract, are strongly associated with the development of colorectal cancer. We used antibiotic perturbations to a murine model of inflammation-driven colon cancer to generate eight starting communities that resulted in various severities of tumorigenesis. Furthermore, we were able to quantitatively predict the final number of tumors on the basis of the initial composition of the gut microbiota. These results further bolster the evidence that the gut microbiota is involved in mediating the development of colorectal cancer. As a final proof of principle, we showed that perturbing the gut microbiota in the midst of tumorigenesis could halt the formation of additional tumors. Together, alteration of the gut microbiota may be a useful therapeutic approach to preventing and altering the trajectory of colorectal cancer. There is growing evidence that individuals with colonic adenomas and carcinomas harbor a distinct microbiota. Alterations to the gut microbiota may allow the outgrowth of bacterial populations that induce genomic mutations or exacerbate tumor-promoting inflammation. In addition, it is likely that the loss of key bacterial populations may result in the loss of protective functions that are normally provided by the microbiota. We explored the role of the gut microbiota in colon tumorigenesis by using an inflammation-based murine model. We observed that perturbing the microbiota with different combinations of antibiotics reduced the number of tumors at the end of the model. Using the random forest machine learning algorithm, we successfully modeled the number of tumors that developed over the course of the model on the basis of the initial composition of the microbiota. The timing of antibiotic treatment was an important determinant of tumor outcome, as colon tumorigenesis was arrested by the use of antibiotics during the early inflammation period of the murine model. Together, these results indicate that it is possible to predict colon tumorigenesis on the basis of the composition of the microbiota and that altering the gut microbiota can alter the course of tumorigenesis. IMPORTANCE Mounting evidence indicates that alterations to the gut microbiota, the complex community of bacteria that inhabits the gastrointestinal tract, are strongly associated with the development of colorectal cancer. We used antibiotic perturbations to a murine model of inflammation-driven colon cancer to generate eight starting communities that resulted in various severities of tumorigenesis. Furthermore, we were able to quantitatively predict the final number of tumors on the basis of the initial composition of the gut microbiota. These results further bolster the evidence that the gut microbiota is involved in mediating the development of colorectal cancer. As a final proof of principle, we showed that perturbing the gut microbiota in the midst of tumorigenesis could halt the formation of additional tumors. Together, alteration of the gut microbiota may be a useful therapeutic approach to preventing and altering the trajectory 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 The gut microflora assay in patients with colorectal cancer: in feces or tissue samples?

2019 ◽  
Author(s):  
Sama Rezasoltani ◽  
Hossein Dabiri ◽  
Hamid Asadzadeh-Aghdaei ◽  
Abbas Akhavan Sepahi ◽  
Mohammad Hossein Modarressi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiota ◽  
Screening Tests ◽  
Microbial Composition ◽  
Tissue Samples ◽  
Bacterial Populations ◽  
Patients With Cancer ◽  
Advantages And Disadvantages ◽  
Identification Of Bacteria ◽  
Tissue Specimens

Gut microbiota is the complex community of microorganisms that live in the digestive tracts of humans and other animals, including insects. The relationship between gut microbiota and human health is mutualistic and altered bacterial composi- tions in fecal and mucosal specimens of colon in patients with cancer compared to healthy subjects were observed. Thereby, studying the gut microbiota, their interactions with the host and their alterations in colorectal cancer (CRC) patients could be helpful to diagnose and treat the disease in earlier stages. In CRC research, the most common samples are feces and tumor tissues. Interestingly, scientists have quite different views regarding gut microbiota composition of feces and tissues. Some believe bacterial populations in feces and mucosa are completely distinct and differ in composition and diversity while some others declare similar variations. Actually, both types of specimens have some advantages and disadvantages in survey of gut microbiota. Fecal samples serve as a noninvasive approach for screening tests while mucosal associated samples are more powerful for identification of bacteria with adenoma and CRC initiation and growth. Here we have discussed the advantages and disadvantages of two type of specimens in CRC investigations and also discussed the similarities and differences of microbial composition between stool and tissue specimens.

scholarly journals Gut Microbiota Influences Experimental Outcomes in Mouse Models of Colorectal Cancer

Genes ◽  
2019 ◽  
Vol 10 (11) ◽  
pp. 900 ◽  
Author(s):  
Alyssa A. Leystra ◽  
Margie L. Clapper
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Experimental Design ◽  
Gut Microbiota ◽  
Mouse Models ◽  
Therapeutic Strategies ◽  
Response To Therapy ◽  
Valuable Resource ◽  
Disease Phenotypes ◽  
Experimental Findings

Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. Mouse models are a valuable resource for use throughout the development and testing of new therapeutic strategies for CRC. Tumorigenesis and response to therapy in humans and mouse models alike are influenced by the microbial communities that colonize the gut. Differences in the composition of the gut microbiota can confound experimental findings and reduce the replicability and translatability of the resulting data. Despite this, the contribution of resident microbiota to preclinical tumor models is often underappreciated. This review does the following: (1) summarizes evidence that the gut microbiota influence CRC disease phenotypes; (2) outlines factors that can influence the composition of the gut microbiota; and (3) provides strategies that can be incorporated into the experimental design, to account for the influence of the microbiota on intestinal phenotypes in mouse models of CRC. Through careful experimental design and documentation, mouse models can continue to rapidly advance efforts to prevent and treat colon cancer.

scholarly journals The Relationship between Prevention and Treatment of Colorectal Cancer and Cancerous Toxin Pathogenesis Theory Basing on Gut Microbiota

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Tianqing Sang ◽  
Wenli Qiu ◽  
Wenting Li ◽  
Hongli Zhou ◽  
Haibin Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Clinical Practice ◽  
Gut Microbiota ◽  
Malignant Tumors ◽  
Tumor Development ◽  
Technological Advances ◽  
Herbal Compound ◽  
Chinese Herbal Compound ◽  
The Relationship

Gut microbiota is a diverse consortium of bacteria, fungi, protozoa, and viruses in the gut of all mammals. Gut microbiota remains in steady state under normal conditions. Changes in the internal and external environment may cause gut Microbiota to be out of tune. Malignant tumors are one of the major diseases currently endangering human health. CRC (colorectal cancer) has a significant upward trend in morbidity and mortality in many parts of the world. Technological advances have not yet brought about a breakthrough in the efficacy of CRC. The development of colon cancer is closely related to gut microbiota imbalance. According to more than 60 years of clinical practice, Professor Zhongying Zhou first proposed the pathogenesis theory of “cancerous toxin” in the 1990s and believed that cancerous toxin was a key pathogenesis of tumor development. Under the guidance of the theory of cancerous toxin, combined with clinical practice, Professor Zhou created an effective anticancer Chinese herbal compound, Jiedu Xiaoai Prescription. This paper summarizes recent hotspots related to gut microbiota and the occurrence, development, and prevention of colon cancer at home and abroad. The relationship between gut microbiota and cancerous toxin theory is proposed, and the feasibility of further studying the biological basis of cancerous toxin pathogenesis theory from the perspective of gut microbiota is pointed out.

scholarly journals The impact of gut microbiota manipulation with antibiotics on colon tumorigenesis in a murine model

PLoS ONE ◽  
2019 ◽  
Vol 14 (12) ◽  
pp. e0226907 ◽  
Author(s):  
Jae Gon Lee ◽  
Chang Soo Eun ◽  
Su Vin Jo ◽  
A-reum Lee ◽  
Chan Hyuk Park ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Murine Model ◽  
Colon Tumorigenesis ◽  
The Impact

Polysaccharides isolated from Nostoc commune Vaucher inhibit colitis-associated colon tumorigenesis in mice and modulate gut microbiota

2019 ◽  
Vol 10 (10) ◽  
pp. 6873-6881 ◽  
Author(s):  
Min Guo ◽  
Zhuoyu Li
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiota ◽  
Nostoc Commune ◽  
Colon Tumorigenesis

NVPS inhibits colorectal cancer in mice and modulates gut microbiota.

scholarly journals The Role of the Gut Microbiome in Colorectal Cancer Development and Therapy Response

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1406 ◽  
Author(s):  
Lidia Sánchez-Alcoholado ◽  
Bruno Ramos-Molina ◽  
Ana Otero ◽  
Aurora Laborda-Illanes ◽  
Rafael Ordóñez ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Fatty Acids ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Cancer Metabolism ◽  
Bacterial Species ◽  
Therapy Response ◽  
Short Chain Fatty Acids ◽  
Bacterial Populations ◽  
High Fiber

Colorectal cancer (CRC) is the third most common cancer worldwide and the leading cause of cancer-related deaths. Recently, several studies have demonstrated that gut microbiota can alter CRC susceptibility and progression by modulating mechanisms such as inflammation and DNA damage, and by producing metabolites involved in tumor progression or suppression. Dysbiosis of gut microbiota has been observed in patients with CRC, with a decrease in commensal bacterial species (butyrate-producing bacteria) and an enrichment of detrimental bacterial populations (pro-inflammatory opportunistic pathogens). CRC is characterized by altered production of bacterial metabolites directly involved in cancer metabolism including short-chain fatty acids and polyamines. Emerging evidence suggests that diet has an important impact on the risk of CRC development. The intake of high-fiber diets and the supplementation of diet with polyunsaturated fatty acids, polyphenols and probiotics, which are known to regulate gut microbiota, could be not only a potential mechanism for the reduction of CRC risk in a primary prevention setting, but may also be important to enhance the response to cancer therapy when used as adjuvant to conventional treatment for CRC. Therefore, a personalized modulation of the pattern of gut microbiome by diet may be a promising approach to prevent the development and progression of CRC and to improve the efficacy of antitumoral therapy.

scholarly journals A Mediterranean Diet Mix Has Chemopreventive Effects in a Murine Model of Colorectal Cancer Modulating Apoptosis and the Gut Microbiota

2019 ◽  
Vol 9 ◽  
Author(s):  
Giulia Piazzi ◽  
Anna Prossomariti ◽  
Maurizio Baldassarre ◽  
Claudio Montagna ◽  
Paola Vitaglione ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiota ◽  
Mediterranean Diet ◽  
Murine Model

scholarly journals Antibiotic-Induced Alterations of the Murine Gut Microbiota and Subsequent Effects on Colonization Resistance against Clostridium difficile

mBio ◽  
2015 ◽  
Vol 6 (4) ◽  
Author(s):  
Alyxandria M. Schubert ◽  
Hamide Sinani ◽  
Patrick D. Schloss
Keyword(s):  
Clostridium Difficile ◽  
Gut Microbiota ◽  
Normal Structure ◽  
The United States ◽  
Context Dependency ◽  
Dependent Manner ◽  
Colonization Resistance ◽  
Bacterial Populations ◽  
Content Type ◽  
Antibiotic Perturbations

ABSTRACTPerturbations to the gut microbiota can result in a loss of colonization resistance against gastrointestinal pathogens such asClostridium difficile. AlthoughC. difficileinfection is commonly associated with antibiotic use, the precise alterations to the microbiota associated with this loss in function are unknown. We used a variety of antibiotic perturbations to generate a diverse array of gut microbiota structures, which were then challenged withC. difficilespores. Across these treatments we observed thatC. difficileresistance was never attributable to a single organism, but rather it was the result of multiple microbiota members interacting in a context-dependent manner. Using relative abundance data, we built a machine learning regression model to predict the levels ofC. difficilethat were found 24 h after challenging the perturbed communities. This model was able to explain 77.2% of the variation in the observed number ofC. difficileper gram of feces. This model revealed important bacterial populations within the microbiota, which correlation analysis alone did not detect. Specifically, we observed that populations associated with thePorphyromonadaceae,Lachnospiraceae,Lactobacillus, andAlistipeswere protective and populations associated withEscherichiaandStreptococcuswere associated with high levels of colonization. In addition, a population affiliated with theAkkermansiaindicated a strong context dependency on other members of the microbiota. Together, these results indicate that individual bacterial populations do not drive colonization resistance toC. difficile. Rather, multiple diverse assemblages act in concert to mediate colonization resistance.IMPORTANCEThe gastrointestinal tract harbors a complex community of bacteria, known as the microbiota, which plays an integral role preventing its colonization by gut pathogens. This resistance has been shown to be crucial for protection againstClostridium difficileinfections (CDI), which are the leading source of hospital-acquired infections in the United States. Antibiotics are a major risk factor for acquiring CDI due to their effect on the normal structure of the indigenous gut microbiota. We found that diverse antibiotic perturbations gave rise to altered communities that varied in their susceptibility toC. difficilecolonization. We found that multiple coexisting populations, not one specific population of bacteria, conferred resistance. By understanding the relationships betweenC. difficileand members of the microbiota, it will be possible to better manage this important infection.

scholarly journals The Gut Microbiome Modulates Colon Tumorigenesis

mBio ◽  
2013 ◽  
Vol 4 (6) ◽  
Author(s):  
Joseph P. Zackular ◽  
Nielson T. Baxter ◽  
Kathryn D. Iverson ◽  
William D. Sadler ◽  
Joseph F. Petrosino ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Gut Microbiome ◽  
Tumor Development ◽  
Tumor Formation ◽  
Normal Functioning ◽  
Operational Taxonomic Units ◽  
Tumor Bearing ◽  
Colon Tumorigenesis

ABSTRACT Recent studies have shown that individuals with colorectal cancer have an altered gut microbiome compared to healthy controls. It remains unclear whether these differences are a response to tumorigenesis or actively drive tumorigenesis. To determine the role of the gut microbiome in the development of colorectal cancer, we characterized the gut microbiome in a murine model of inflammation-associated colorectal cancer that mirrors what is seen in humans. We followed the development of an abnormal microbial community structure associated with inflammation and tumorigenesis in the colon. Tumor-bearing mice showed enrichment in operational taxonomic units (OTUs) affiliated with members of the Bacteroides, Odoribacter, and Akkermansia genera and decreases in OTUs affiliated with members of the Prevotellaceae and Porphyromonadaceae families. Conventionalization of germfree mice with microbiota from tumor-bearing mice significantly increased tumorigenesis in the colon compared to that for animals colonized with a healthy gut microbiome from untreated mice. Furthermore, at the end of the model, germfree mice colonized with microbiota from tumor-bearing mice harbored a higher relative abundance of populations associated with tumor formation in conventional animals. Manipulation of the gut microbiome with antibiotics resulted in a dramatic decrease in both the number and size of tumors. Our results demonstrate that changes in the gut microbiome associated with inflammation and tumorigenesis directly contribute to tumorigenesis and suggest that interventions affecting the composition of the microbiome may be a strategy to prevent the development of colon cancer. IMPORTANCE The trillions of bacteria that live in the gut, known collectively as the gut microbiome, are important for normal functioning of the intestine. There is now growing evidence that disruptive changes in the gut microbiome are strongly associated with the development colorectal cancer. However, how the gut microbiome changes with time during tumorigenesis and whether these changes directly contribute to disease have not been determined. We demonstrate using a mouse model of inflammation-driven colon cancer that there are dramatic, continual alterations in the microbiome during the development of tumors, which are directly responsible for tumor development. Our results suggest that interventions that target these changes in the microbiome may be an effective strategy for preventing the development of colorectal cancer.

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