The Gut Microbiome Modulates Colon Tumorigenesis
By Joseph P. Zackular, Nielson T. Baxter, Kathryn Iverson, W. D. Sadler, J. Petrosino, Grace Y. Chen, Patrick D. Schloss. mBio, 2013
668 citations recorded by the source corpus.
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. 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.
Subfields: Biotechnology, Infectious Diseases, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/b6c598c2c91384db0250341b814faf61081cc776
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Citations in the corpus
- The microbiome and cancer (2018, methodology): “Advancing this work in an azoxymethane (AOM)/dextran sulphate sodium (DSS) tumour model, Zackular et al [36] demonstrated that the microbiota of tumour-bearing mice, when transmitted to germ-free recipients, resulted in faster onset and greater severity of colorectal tumours than microbiome transmit”
- Wild Mouse Gut Microbiota Promotes Host Fitness and Improves Disease Resistance (2017, neutral): “It is well known that the bacterial gut microbiome affects disease outcomes in influenza virus infection (Abt et al., 2012; Ichinohe et al., 2011; Oh et al., 2014) and colorectal tumorigenesis models (Zackular et al., 2013, 2016).”
- Disease-specific Alterations in the Enteric Virome in Inflammatory Bowel Disease (2015, background): “These include diabetes, obesity, metabolic diseases, and cancer (Larsen et al., 2010; Ley et al., 2005; Nicholson et al., 2012; Qin et al., 2012; Shen et al., 2010; Turnbaugh et al., 2006, 2009; Zackular et al., 2013).”
- Colorectal Carcinoma: A General Overview and Future Perspectives in Colorectal Cancer (2017, background): “Another proposed mechanism for the onset of CRC is the presence of bacterial secondary metabolites, such as reactive oxygen intermediates or some kinds of toxins, which can damage host DNA and induce cell transformation [153–157].”
- Current understanding of dysbiosis in disease in human and animal models (2016, background): “The manipulation of the intestinal microbiota with antibiotic treatment also demonstrated the importance of the microbiota in tumor status, showing a decrease in number and size of tumors in CRC-susceptible mice when antibiotics were administered.(41,44) Experiments in MyD88-deficient mice showed a ”