Epigenetic Effects of Gut Microbiota on Obesity and Gastrointestinal Cancers

The microbial census within our gastrointestinal tract outnumbers our own cells by roughly tenfold. Our gastrointestinal microbiota performs many important roles including contributing to the energy harvest from our diet, protecting us from colonization b

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Epigenetic Effects of Gut Microbiota on Obesity and Gastrointestinal Cancers Joice Kuroiwa-Trzmielina and Luke B. Hesson

Abstract The microbial census within our gastrointestinal tract outnumbers our own cells by roughly tenfold. Our gastrointestinal microbiota performs many important roles including contributing to the energy harvest from our diet, protecting us from colonization by pathogenic species of bacteria, eliminating harmful metabolites and carcinogens, and shaping our immune system to prevent chronic mucosal inflammation. Given these important functions, as well as the shear abundance of bacteria within our gastrointestinal tract, it seems intuitive that our microbiota must play some role in disease. Many studies have described changes in the gastrointestinal microbiota in various disease states including cancer, inflammatory bowel disease, diabetes, and obesity. However, important questions remain; are these changes in the microbiota a cause or consequence of disease, or are they merely correlative? If changes in the gastrointestinal microbiota are a potential cause of disease, then what's the mechanism? Here we consider the evidence that the gastrointestinal microbiota can induce epigenetic changes in host cells and whether this is a potential contributing factor to obesity and gastrointestinal cancers. Keywords Microbiota • Microbiome • Epigenetic • Methylation • Histone • Metabolites • Cancer • Gastrointestinal • Dysbiosis

Introduction The term gastrointestinal microbiota refers to the bacteria, archaea, viruses, protozoa, helminths, and fungi that inhabit the gastrointestinal tract, whereas the term microbiome refers to the collective genomes of these microorganisms. The gastrointestinal tract of a healthy human contains around 100 trillion microorganisms, which exceeds the J. Kuroiwa-Trzmielina Garvan Institute of Medical Research, Kinghorn Centre for Clinical Genomics, Sydney, NSW 2010, Australia L.B. Hesson (*) Adult Cancer Program, Lowy Cancer Research Centre and Prince of Wales Clinical School, UNSW Australia, Sydney, NSW 2052, Australia e-mail: [email protected] © Springer International Publishing Switzerland 2016 N.A. Berger (ed.), Epigenetics, Energy Balance, and Cancer, Energy Balance and Cancer 11, DOI 10.1007/978-3-319-41610-6_7

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J. Kuroiwa-Trzmielina and L.B. Hesson

total number of human cells in the body by a factor of ~10. Between 1000 and 1150 bacterial species have been identified in human feces, with around 160 species shared between most individuals [1]. Our gastrointestinal microbiota consists of 99.1 % bacteria and is comprised of four major microbial phyla: Firmicutes, 30.6–83 % (Clostridium, Ruminococcus, Eubacterium, Dorea, Peptostreptococcus, Peptococcus, Lactobacillus); Bacteroidetes, 8–48 % (Bacteroides); Proteobacteria, 0.1–26.6 % (Enterobacteriaceae); and Actinobacteria, 0.7–16.7 % (Bifidobacterium) [1–3]. The composition of the gut microbiota is shaped by multiple factors including diet, medications (such as antibiotics), sanitization, animal exposure, h