Environmental Influences in the Etiology of Colorectal Cancer: the Premise of Metabolomics

Rattray, Nicholas A.; Charkoftaki, Georgia; Rattray, Zahra; Hansen, James E.; Vasiliou, Vasilis; Johnson, Caroline H.

doi:10.1007/s40495-017-0088-z

Cited by 58 publications

(41 citation statements)

References 132 publications

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“…It is vital that a more comprehensive understanding of how these environmental exposures affect biology at the systems level to determine cause, effect, and susceptibilities. In doing so, a compound specific “exposotype” can be developed that accounts for the totality of the multileveled downstream biological changes that an individual exposure event produces [ 18 ]. To better understand these effects, metabolomics can be used to develop not only metabolic biomarkers of exposure but can also be used to build metabolic models that identify upstream genetic and enzymatic changes.…”

Section: Discussionmentioning

confidence: 99%

“…Multi-omics approaches using combined data from genomics, proteomics, and metabolomics techniques can identify downstream chemical alterations contributing to the development of an exposotype, the exposure phenotype (Fig. 1 ), that describes the accrued biological changes within a system that has undergone a specific exposure event [ 18 ] . Combining information from all levels of protein synthesis and subsequent enzymatic action on metabolite production is an essential step to start comprehending the complex global modulating effect that an exposure event has on an individual phenotype.…”

Section: Application Of High-dimensional Biology To the Environmentalmentioning

confidence: 99%

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Beyond genomics: understanding exposotypes through metabolomics

Rattray

Deziel

Wallach³

et al. 2018

Hum Genomics

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BackgroundOver the past 20 years, advances in genomic technology have enabled unparalleled access to the information contained within the human genome. However, the multiple genetic variants associated with various diseases typically account for only a small fraction of the disease risk. This may be due to the multifactorial nature of disease mechanisms, the strong impact of the environment, and the complexity of gene-environment interactions. Metabolomics is the quantification of small molecules produced by metabolic processes within a biological sample. Metabolomics datasets contain a wealth of information that reflect the disease state and are consequent to both genetic variation and environment. Thus, metabolomics is being widely adopted for epidemiologic research to identify disease risk traits. In this review, we discuss the evolution and challenges of metabolomics in epidemiologic research, particularly for assessing environmental exposures and providing insights into gene-environment interactions, and mechanism of biological impact.Main textMetabolomics can be used to measure the complex global modulating effect that an exposure event has on an individual phenotype. Combining information derived from all levels of protein synthesis and subsequent enzymatic action on metabolite production can reveal the individual exposotype. We discuss some of the methodological and statistical challenges in dealing with this type of high-dimensional data, such as the impact of study design, analytical biases, and biological variance. We show examples of disease risk inference from metabolic traits using metabolome-wide association studies. We also evaluate how these studies may drive precision medicine approaches, and pharmacogenomics, which have up to now been inefficient. Finally, we discuss how to promote transparency and open science to improve reproducibility and credibility in metabolomics.ConclusionsComparison of exposotypes at the human population level may help understanding how environmental exposures affect biology at the systems level to determine cause, effect, and susceptibilities. Juxtaposition and integration of genomics and metabolomics information may offer additional insights. Clinical utility of this information for single individuals and populations has yet to be routinely demonstrated, but hopefully, recent advances to improve the robustness of large-scale metabolomics will facilitate clinical translation.

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Section: Discussionmentioning

confidence: 99%

Section: Application Of High-dimensional Biology To the Environmentalmentioning

confidence: 99%

Beyond genomics: understanding exposotypes through metabolomics

Rattray

Deziel

Wallach³

et al. 2018

Hum Genomics

Self Cite

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“…There are increased evidences that environmental factors such as lifestyle and diet alterations have effect in CRC incidence [30]. This effect has been documented because there is evidence showing an essential relationship between dietary antigens and antigens of commensal bacteria with the regulatory T cells (Tregs), which maintain the immune tolerance and, consequently, reduce the risk of tumorigenesis associated with inflammation [31].…”

Section: Ibd Complications and Microbiota Manipulationmentioning

confidence: 99%

Recombinant Probiotics and Microbiota Modulation as a Good Therapy for Diseases Related to the GIT

Jesus¹,

Lima²,

Coelho-Rocha³

et al. 2020

The Health Benefits of Foods - Current Knowledge and Further Development

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Many diseases that affect the gastrointestinal tract (GIT) have great influence on the quality of life of the majority of patients. Many probiotic strains are being highly studied as a promising candidate due to their beneficial effect reported in the GIT. With the purpose of increasing the beneficial characteristics of some probiotics strains and, consequently, to improve further the reported results, many probiotic strains expressing or encoding different proteins, with anti-inflammatory activities, have been developed. These recombinant strains have been reported as good candidates for the treatment of different pathological conditions, especially colitis and mucositis disease since they have been shown to have positive results and good perspectives for GIT inflammation. Thus, this chapter will first address the aspects of the gastrointestinal tract in humans as well as its microbiota. In a second moment, it will discuss about chronic diseases, mainly the intestinal ones. Finally, it will discuss about probiotics, especially concerning on lactic acid bacteria (LAB), and its action in the prevention and treatment of these diseases. At the final part, we will point out aspects on the development of recombinant strains and the results found in the literature on disease models.

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“…New technologies allowed the identification of new biomarkers and their co-evolution with drug discovery and targeted therapies design. Importantly, cancer susceptibility does not just depend on the genetic background of patients; environmental factors as well as lifestyle are determinants in the etiology of CRC [ 81 ]. Despite the improvements in early diagnosis and targeted therapies design for CRC, the rates of its incidence have been increasing for people younger than 40 years, pointing out the pressing needs for identifying the underlying environmental factors and providing preventive strategies for high-risk individuals [ 82 ].…”

Section: Nutrition and Colorectal Cancermentioning

confidence: 99%

Precision Nutrition for Targeting Lipid Metabolism in Colorectal Cancer

2017

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Cancer is a multistage and multifactorial condition with genetic and environmental factors modulating tumorogenesis and disease progression. Nevertheless, cancer is preventable, as one third of cancer deaths could be avoided by modifying key risk factors. Nutrients can directly affect fundamental cellular processes and are considered among the most important risk factors in colorectal cancer (CRC). Red and processed meat, poultry consumption, fiber, and folate are the best-known diet components that interact with colorectal cancer susceptibility. In addition, the direct association of an unhealthy diet with obesity and dysbiosis opens new routes in the understanding of how daily diet nutrients could influence cancer prognosis. In the “omics” era, traditional nutrition has been naturally evolved to precision nutrition where technical developments have contributed to a more accurate discipline. In this sense, genomic and transcriptomic studies have been extensively used in precision nutrition approaches. However, the relation between CRC carcinogenesis and nutrition factors is more complex than originally expected. Together with classical diet-nutrition-related genes, nowadays, lipid-metabolism-related genes have acquired relevant interest in precision nutrition studies. Lipids regulate very diverse cellular processes from ATP synthesis and the activation of essential cell-signaling pathways to membrane organization and plasticity. Therefore, a wide range of tumorogenic steps can be influenced by lipid metabolism, both in primary tumours and distal metastasis. The extent to which genetic variants, together with the intake of specific dietary components, affect the risk of CRC is currently under investigation, and new therapeutic or preventive applications must be explored in CRC models. In this review, we will go in depth into the study of co-occurring events, which orchestrate CRC tumorogenesis and are essential for the evolution of precision nutrition paradigms. Likewise, we will discuss the application of precision nutrition approaches to target lipid metabolism in CRC.

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Environmental Influences in the Etiology of Colorectal Cancer: the Premise of Metabolomics

Cited by 58 publications

References 132 publications

Beyond genomics: understanding exposotypes through metabolomics

Beyond genomics: understanding exposotypes through metabolomics

Recombinant Probiotics and Microbiota Modulation as a Good Therapy for Diseases Related to the GIT

Precision Nutrition for Targeting Lipid Metabolism in Colorectal Cancer

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