The gut microbiota and colon cancer Garrett, Wendy S
Science (American Association for the Advancement of Science),
06/2019, Letnik:
364, Številka:
6446
Journal Article
Recenzirano
Microbiome data should be incorporated into the prevention, diagnosis, and treatment of colon cancer
The human microbiota is the collection of microorganisms—bacteria, archaea, viruses, fungi, ...protozoa, and helminths—that populate the human body. They are emerging as an important feature of human health and disease. Currently, access to the genomic data of human cells and of microbiota (microbiomes) is more affordable and accessible than ever before. A major challenge is to unravel how we integrate microbiome data into precision medicine approaches for the prevention, diagnosis, and treatment of diseases such as cancer. The gastrointestinal (GI) tract is densely populated with microorganisms. Colorectal cancer (CRC) is the third most prevalent cancer worldwide. It is increasing in individuals less than 50 years old and is associated with specific dietary factors and eating patterns that affect the gut microbiota. Therefore, CRC seems ripe for microbiome-based prevention, diagnostics, and therapeutics.
Cancer and the microbiota Garrett, Wendy S.
Science,
04/2015, Letnik:
348, Številka:
6230
Journal Article
Recenzirano
Odprti dostop
A host's microbiota may increase, diminish, or have no effect at all on cancer susceptibility. Assigning causal roles in cancer to specific microbes and microbiotas, unraveling host-microbiota ...interactions with environmental factors in carcinogenesis, and exploiting such knowledge for cancer diagnosis and treatment are areas of intensive interest. This Review considers how microbes and the microbiota may amplify or mitigate carcinogenesis, responsiveness to cancer therapeutics, and cancer-associated complications.
Fusobacterium nucleatum has long been found to cause opportunistic infections and has recently been implicated in colorectal cancer; however, it is a common member of the oral microbiota and can have ...a symbiotic relationship with its hosts. To address this dissonance, we explore the diversity and niches of fusobacteria and reconsider historic fusobacterial taxonomy in the context of current technology. We also undertake a critical reappraisal of fusobacteria with a focus on F. nucleatum as a mutualist, infectious agent and oncogenic microorganism. In this Review, we delve into recent insights and future directions for fusobacterial research, including the current genetic toolkit, our evolving understanding of its mechanistic role in promoting colorectal cancer and the challenges of developing diagnostics and therapeutics for F. nucleatum.
The microbiota - the collection of microorganisms that live within and on all mammals - provides crucial signals for the development and function of the immune system. Increased availability of ...technologies that profile microbial communities is facilitating the entry of many immunologists into the evolving field of host-microbiota studies. The microbial communities, their metabolites and components are not only necessary for immune homeostasis, they also influence the susceptibility of the host to many immune-mediated diseases and disorders. In this Review, we discuss technological and computational approaches for investigating the microbiome, as well as recent advances in our understanding of host immunity and microbial mutualism with a focus on specific microbial metabolites, bacterial components and the immune system.
Colorectal cancer is the second-leading cause of cancer-related deaths in the United States and fourth-leading cause of cancer-related deaths worldwide. While cancer is largely considered to be a ...disease of genetic and environmental factors, increasing evidence has demonstrated a role for the microbiota (the microorganisms associated with the human body) in shaping inflammatory environments and promoting tumor growth and spread. Herein, we discuss both human data from meta'omics analyses and data from mechanistic studies in cell culture and animal models that support specific bacterial agents as potentiators of tumorigenesis-including
Fusobacterium nucleatum
, enterotoxigenic
Bacteroides fragilis
, and colibactin-producing
Escherichia coli
. Further, we consider how microbes can be used in diagnosing colorectal cancer and manipulating the tumor environment to encourage better patient outcomes in response to immunotherapy treatments.
Cancer cells originate from a series of acquired genetic mutations that can drive their uncontrolled cell proliferation and immune evasion. Environmental factors, including the microorganisms that ...colonize the human body, can shift the metabolism, growth pattern and function of neoplastic cells and shape the tumour microenvironment. Dysbiosis of the gut microbiome is now recognized as a hallmark of cancer by the scientific community. However, only a few microorganisms have been identified that directly initiate tumorigenesis or skew the immune system to generate a tumour-permissive milieu. Over the past two decades, research on the human microbiome and its functionalities within and across individuals has revealed microbiota-focused strategies for health and disease. Here, we review the evolving understanding of the mechanisms by which the microbiota acts in cancer initiation, promotion and progression. We explore the roles of bacteria in gastrointestinal tract malignancies and cancers of the lung, breast and prostate. Finally, we discuss the promises and limitations of targeting or harnessing bacteria in personalized cancer prevention, diagnostics and treatment.
Colorectal cancer (CRC) presents a considerable disease burden worldwide. The human colon is also an anatomical location with the largest number of microbes. It is natural, therefore, to anticipate a ...role for microbes, particularly bacteria, in colorectal carcinogenesis. The increasing accessibility of microbial meta’omics is fueling a surge in our understanding of the role that microbes and the microbiota play in CRC. In this review, we will discuss recent insights into contributions of the microbiota to CRC and explore conceptual frameworks for evaluating the role of microbes in cancer causation. We also highlight new findings on candidate CRC-potentiating species and current knowledge gaps. Finally, we explore the roles of microbial metabolism as it relates to bile acids, xenobiotics, and diet in the etiology and therapeutics of CRC.
Sears and Garrett review recent insights into the contributions of microbes and microbiota to colorectal cancer (CRC). Specifically, they explore conceptual frameworks for assigning a cancer-causing role for microbes, highlight candidate CRC-potentiating microbial species, and explore the roles of microbial metabolism in the etiology and therapeutics of CRC.
Diet has an important role in the development of colorectal cancer. In the past few decades, findings from extensive epidemiologic and experimental investigations have linked consumption of several ...foods and nutrients to the risk of colorectal neoplasia. Calcium, fiber, milk, and whole grains have been associated with a lower risk of colorectal cancer, and red meat and processed meat have been associated with an increased risk. There is substantial evidence for the potential chemopreventive effects of vitamin D, folate, fruits, and vegetables. Nutrients and foods also may interact, as a dietary pattern, to influence colorectal cancer risk. Diet likely influences colorectal carcinogenesis through several interacting mechanisms. These include the direct effects on immune responsiveness and inflammation, and the indirect effects of overnutrition and obesity—risk factors for colorectal cancer. Emerging evidence also implicates the gut microbiota as an important effector in the relationship between diet and cancer. Dietary modification therefore has the promise of reducing colorectal cancer incidence.
The importance of the microbiota in the development of colorectal cancer (CRC) is increasingly evident, but identifying specific microbial features that influence CRC initiation and progression ...remains a central task for investigators. Studies determining the microbial mechanisms that directly contribute to CRC development or progression are revealing bacterial factors such as toxins that contribute to colorectal carcinogenesis. However, even when investigators have identified bacteria that express toxins, questions remain about the host determinants of a toxin's cancer-potentiating effects. For other cancer-correlating bacteria that lack toxins, the challenge is to define cancer-relevant virulence factors. Herein, we evaluate three CRC-correlating bacteria, colibactin-producing Escherichia coli, enterotoxigenic Bacteroides fragilis, and Fusobacterium nucleatum, for their virulence features relevant to CRC. We also consider the beneficial bioactivity of gut microbes by highlighting a microbial metabolite that may enhance CRC antitumor immunity. In doing so, we aim to elucidate unique and shared mechanisms underlying the microbiota's contributions to CRC and to accelerate investigation from target validation to CRC therapeutic discovery.
PDF
