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      Gut Microbiota Imbalance and Base Excision Repair Dynamics in Colon Cancer

      review-article
      Author(s): , ✉
      Publication date (Electronic):
      Journal: Journal of Cancer
      Publisher: Ivyspring International Publisher
      Keywords: Microbiota, Base excision repair, Colon cancer.

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          Abstract

          Gut microbiota are required for host nutrition, energy balance, and regulating immune homeostasis, however, in some cases, this mutually beneficial relationship becomes twisted (dysbiosis), and the gut flora can incite pathological disorders including colon cancer. Microbial dysbiosis promotes the release of bacterial genotoxins, metabolites, and causes chronic inflammation, which promote oxidative DNA damage. Oxidized DNA base lesions are removed by base excision repair (BER), however, the role of this altered function of BER, as well as microbiota-mediated genomic instability and colon cancer development, is still poorly understood. In this review article, we will discuss how dysbiotic microbiota induce DNA damage, its impact on base excision repair capacity, the potential link of host BER gene polymorphism, and the risk of dysbiotic microbiota mediated genomic instability and colon cancer.

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          Individuality in gut microbiota composition is a complex polygenic trait shaped by multiple environmental and host genetic factors.

          Andrew Benson, Scott Kelly, Ryan M Legge … (2010)
          In vertebrates, including humans, individuals harbor gut microbial communities whose species composition and relative proportions of dominant microbial groups are tremendously varied. Although external and stochastic factors clearly contribute to the individuality of the microbiota, the fundamental principles dictating how environmental factors and host genetic factors combine to shape this complex ecosystem are largely unknown and require systematic study. Here we examined factors that affect microbiota composition in a large (n = 645) mouse advanced intercross line originating from a cross between C57BL/6J and an ICR-derived outbred line (HR). Quantitative pyrosequencing of the microbiota defined a core measurable microbiota (CMM) of 64 conserved taxonomic groups that varied quantitatively across most animals in the population. Although some of this variation can be explained by litter and cohort effects, individual host genotype had a measurable contribution. Testing of the CMM abundances for cosegregation with 530 fully informative SNP markers identified 18 host quantitative trait loci (QTL) that show significant or suggestive genome-wide linkage with relative abundances of specific microbial taxa. These QTL affect microbiota composition in three ways; some loci control individual microbial species, some control groups of related taxa, and some have putative pleiotropic effects on groups of distantly related organisms. These data provide clear evidence for the importance of host genetic control in shaping individual microbiome diversity in mammals, a key step toward understanding the factors that govern the assemblages of gut microbiota associated with complex diseases.
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            The core gut microbiome, energy balance and obesity.

            Peter J. Turnbaugh, Jeffrey Gordon (2009)
            Metagenomics is an emerging field focused on characterizing the structures, functions and dynamic operations of microbial communities sampled in their native habitats without the need for culture. Here, we present findings from a 16S rRNA gene sequence- and whole community DNA shotgun sequencing-based analysis of the adult human gut microbiomes of lean and obese mono- and dizygotic twins. Our findings indicate that a core microbiome can be found at the gene level, despite large variation in community membership, and that variations from the core are associated with obesity. These findings have implications for ongoing Human Microbiome Project(s), and highlight important challenges to the field of metagenomics.
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              Base-excision repair of oxidative DNA damage.

              Sheila David, Valerie O'Shea, Sucharita Kundu (2007)
              Maintaining the chemical integrity of DNA in the face of assault by oxidizing agents is a constant challenge for living organisms. Base-excision repair has an important role in preventing mutations associated with a common product of oxidative damage to DNA, 8-oxoguanine. Recent structural studies have shown that 8-oxoguanine DNA glycosylases use an intricate series of steps to locate and excise 8-oxoguanine lesions efficiently against a high background of undamaged bases. The importance of preventing mutations associated with 8-oxoguanine is shown by a direct association between defects in the DNA glycosylase MUTYH and colorectal cancer. The properties of other guanine oxidation products and the associated DNA glycosylases that remove them are now also being revealed.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Cancer
                Journal ID (iso-abbrev): J Cancer
                Journal ID (publisher-id): jca
                Title: Journal of Cancer
                Publisher: Ivyspring International Publisher (Sydney )
                ISSN (Electronic): 1837-9664
                Publication date Collection: 2016
                Publication date (Electronic): 4 July 2016
                Volume: 7
                Issue: 11
                Pages: 1421-1430
                Affiliations
                Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Dell Pediatric Research Institute, 1400 Barbara Jordan Blvd. R1800, Austin, TX 78723, United States.
                Author notes
                ✉ Corresponding author: Dawit Kidane, Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Dell Pediatric Research Institute, 1400 Barbara Jordan Blvd. Mail code R1800, Austin, TX 78723, United States. Phone: (512) 495-4720 FAX : 512-495-4945 Email: dawit.kidane@ 123456austin.utexas.edu .

                Competing Interests: The authors have no conflict of interest.

                Article
                Publisher ID: jcav07p1421
                DOI: 10.7150/jca.15480
                PMC ID: 4964126
                PubMed ID: 27471558
                SO-VID: 191e6b1c-b5d1-4194-b172-06b309819696
                Copyright © © Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions.
                History
                Date received : 8 March 2016
                Date accepted : 18 May 2016
                Categories
                Subject: Review

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: microbiota,base excision repair,colon cancer.
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: microbiota, base excision repair, colon cancer.

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