The Role of the Intestinal Microbiome on Colorectal Cancer Pathogenesis and its Recurrence Following Surgery
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REVIEW ARTICLE
The Role of the Intestinal Microbiome on Colorectal Cancer Pathogenesis and its Recurrence Following Surgery Janani Vigneswaran 1 & Benjamin D. Shogan 1 Received: 27 May 2020 / Accepted: 4 June 2020 # 2020 The Society for Surgery of the Alimentary Tract
Abstract Colorectal cancer is the result of multiple genetic mutations that drive normal cells to adenoma and then carcinoma. Recent technology has evolved to allow for an in-depth examination of the microbiota and it has become clear that many components of the intestinal microbiome play a role in promoting carcinogenesis. This review aims to describe the potential mechanisms that lead to the dysbiosis that initiates tumor formation and that influence the development of cancer recurrence following surgical resection. We further discuss how manipulation of the microbiome may be a future novel strategy to prevent both primary and secondary colorectal cancer. While we discuss how bacterial communities and individual strains can promote cancer, the microbiome is individualized, dynamic, and complex, and our understanding of its role in carcinogenesis is still in its infancy. Keywords Microbiota . Colorectal neoplasm . Carcinogenesis . Recurrence
Introduction Colorectal cancer (CRC) is a major health problem with nearly two million cases diagnosed worldwide last year.1 Since it was first described in the 1980s by Fearon and Vogelstein, the “adenoma-carcinoma sequence” has been the standard bearer to our understanding of the genetic basis of CRC (Fig. 1a). This model describes that malignant cell proliferation results from the accumulation of multiple genetic mutations leading to activation of oncogenes or inactivation of tumor suppressor genes, driving normal cells to adenoma and then carcinoma.2 While precise triggers of each necessary genetic mutation remain ill-defined, numerous studies have established a clear link between environmental factors and the risk of colon cancer. Because the factors that portend the highest CRC risk, such as cigarette smoking, obesity, consumption of red meat, and inflammatory bowel disease, also greatly influence the composition of the microbiome, it has since been hypothesized that the mechanism by which these environmental factors increase CRC risk is via perturbations of the intestinal 3 organisms . The development of technologies in the early
* Benjamin D. Shogan [email protected] 1
Division of Colon and Rectal Surgery, University of Chicago, Room J557F, MC 5095, 5841 S. Maryland Ave, Chicago, IL 60637, USA
2000s for high-throughput sequencing (next generation sequencing) and culture-independent methods for microbial profiling (16S rRNA sequencing and metagenomics) has allowed for a more comprehensive examination of microbial communities that was previously not possible.4,5 These tools have created an explosion of research into the influence of microbes on the pathogenesis and treatment of CRC. In this review, we provide an overview of the current advances in our understanding of the microbe-cancer
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