The struggle within: Microbial influences on colorectal cancer

&NA; Recently, an unprecedented effort has been directed at understanding the interplay between chronic inflammation and development of cancer, with the case of inflammatory bowel disease (IBD)‐associated colorectal cancer at the forefront of this research endeavor. The last decade has been particularly fertile, with the discovery of numerous innovative paradigms linking various inflammatory, proliferative, and innate and adaptive immune signaling pathways to the development of colorectal cancer. Because of the preponderant role of the intestinal microbiota in the initiation and progression of IBD, recent efforts have been directed at understanding the relationship between bacteria and colorectal cancer. The microbiota and its collective genome, the microbiome, form a diverse and complex ecological community that profoundly impacts intestinal homeostasis and disease states. This review will discuss the differential influence of the microbiota on the development of IBD‐associated colorectal cancer and highlight the role of innate immune sensor‐dependent as well as ‐independent mechanisms in this pathology. (Inflamm Bowel Dis 2011;)

[1]  H. Herfarth,et al.  The NLRP3 inflammasome functions as a negative regulator of tumorigenesis during colitis-associated cancer , 2010, The Journal of experimental medicine.

[2]  H. Herfarth,et al.  476 Intestinal Inflammation is Not Sufficient to Promote the Development of Colitis Associated Colorectal Cancer: Role of the Enteric Microbiota , 2010 .

[3]  P. Bork,et al.  A human gut microbial gene catalogue established by metagenomic sequencing , 2010, Nature.

[4]  B. Finlay,et al.  Host immune response to antibiotic perturbation of the microbiota , 2010, Mucosal Immunology.

[5]  S. Sørensen,et al.  Gut Microbiota in Human Adults with Type 2 Diabetes Differs from Non-Diabetic Adults , 2010, PloS one.

[6]  Youfang Cao,et al.  Interactions between gut microbiota, host genetics and diet relevant to development of metabolic syndromes in mice , 2010, The ISME Journal.

[7]  Zhen-hua Hu,et al.  Differential effects of NOD2 polymorphisms on colorectal cancer risk: a meta-analysis , 2010, International Journal of Colorectal Disease.

[8]  Jeffrey N. Weiser,et al.  Recognition of Peptidoglycan from the Microbiota by Nod1 Enhances Systemic Innate Immunity , 2010, Nature Medicine.

[9]  Fabio Cominelli,et al.  Probiotics promote gut health through stimulation of epithelial innate immunity , 2009, Proceedings of the National Academy of Sciences.

[10]  Patrice D Cani,et al.  Interplay between obesity and associated metabolic disorders: new insights into the gut microbiota. , 2009, Current opinion in pharmacology.

[11]  Dan R. Littman,et al.  Induction of Intestinal Th17 Cells by Segmented Filamentous Bacteria , 2009, Cell.

[12]  R. Xavier,et al.  Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43 , 2009, Nature.

[13]  G. Weinstock,et al.  Enteric defensins are essential regulators of intestinal microbial ecology , 2009, Nature Immunology.

[14]  Michael Krawczak,et al.  Investigation of innate immunity genes CARD4, CARD8 and CARD15 as germline susceptibility factors for colorectal cancer , 2009, BMC gastroenterology.

[15]  F. Taieb,et al.  The Enteropathogenic Escherichia coli Effector Cif Induces Delayed Apoptosis in Epithelial Cells , 2009, Infection and Immunity.

[16]  W. Strober The multifaceted influence of the mucosal microflora on mucosal dendritic cell responses. , 2009, Immunity.

[17]  Tomas Hrncir,et al.  Nod2 is required for the regulation of commensal microbiota in the intestine , 2009, Proceedings of the National Academy of Sciences.

[18]  G. Eberl,et al.  The development of intestinal lymphoid tissues at the interface of self and microbiota , 2009, Mucosal Immunology.

[19]  Graham M Lord,et al.  Colitis-associated colorectal cancer driven by T-bet deficiency in dendritic cells. , 2009, Cancer cell.

[20]  P. Turnbaugh,et al.  The core gut microbiome, energy balance and obesity , 2009, The Journal of physiology.

[21]  Cynthia L Sears,et al.  A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses , 2009, Nature Medicine.

[22]  Zhiheng Pei,et al.  Inflammation and intestinal metaplasia of the distal esophagus are associated with alterations in the microbiome. , 2009, Gastroenterology.

[23]  Thomas F. Tedder,et al.  Innate and Adaptive Immunity Cooperate Flexibly to Maintain Host-Microbiota Mutualism , 2009, Science.

[24]  F. Bushman,et al.  Community-Wide Response of the Gut Microbiota to Enteropathogenic Citrobacter rodentium Infection Revealed by Deep Sequencing , 2009, Infection and Immunity.

[25]  C. Jobin,et al.  Microbes and colorectal cancer: is there a relationship? , 2009, Current oncology.

[26]  Rob Knight,et al.  Regulation of myocardial ketone body metabolism by the gut microbiota during nutrient deprivation , 2009, Proceedings of the National Academy of Sciences.

[27]  R. Knight,et al.  Microbial community profiling for human microbiome projects: Tools, techniques, and challenges. , 2009, Genome research.

[28]  Judy H. Cho,et al.  Interleukin-23/Th17 pathways and inflammatory bowel disease. , 2009, Inflammatory bowel diseases.

[29]  R. Xu,et al.  Innate immune signaling by Toll‐like receptor‐4 (TLR4) shapes the inflammatory microenvironment in colitis‐associated tumors , 2009, Inflammatory bowel diseases.

[30]  H. Herfarth,et al.  Modulation of the Intestinal Microbiota Alters Colitis-Associated Colorectal Cancer Susceptibility , 2009, PloS one.

[31]  A. Nowak,et al.  Ability of probiotic Lactobacillus casei DN 114001 to bind or/and metabolise heterocyclic aromatic amines in vitro , 2009, European journal of nutrition.

[32]  James Versalovic,et al.  Targeting the human microbiome with antibiotics, probiotics, and prebiotics: gastroenterology enters the metagenomics era. , 2009, Gastroenterology.

[33]  Patrice D Cani,et al.  The role of the gut microbiota in energy metabolism and metabolic disease. , 2009, Current pharmaceutical design.

[34]  I. Rowland The role of the gastrointestinal microbiota in colorectal cancer. , 2009, Current pharmaceutical design.

[35]  G. Cresci,et al.  GPR109A is a G-protein-coupled receptor for the bacterial fermentation product butyrate and functions as a tumor suppressor in colon. , 2009, Cancer research.

[36]  H. Qin,et al.  L. plantarum prevents Enteroinvasive Escherichia coli-induced tight junction proteins changes in intestinal epithelial cells , 2009, BMC Microbiology.

[37]  F. Taieb,et al.  Cycle Inhibiting Factors (CIFs) Are a Growing Family of Functional Cyclomodulins Present in Invertebrate and Mammal Bacterial Pathogens , 2009, PloS one.

[38]  James Versalovic,et al.  Probiotic Lactobacillus reuteri biofilms produce antimicrobial and anti-inflammatory factors , 2009, BMC Microbiology.

[39]  M. Karin,et al.  IL-6 and Stat3 are required for survival of intestinal epithelial cells and development of colitis-associated cancer. , 2009, Cancer cell.

[40]  L. Hale,et al.  Effects of Helicobacter infection on research: the case for eradication of Helicobacter from rodent research colonies. , 2009, Comparative medicine.

[41]  L. Eckmann,et al.  Paneth cells directly sense gut commensals and maintain homeostasis at the intestinal host-microbial interface , 2008, Proceedings of the National Academy of Sciences.

[42]  Gabriel Núñez,et al.  The innate immune receptor Nod1 protects the intestine from inflammation-induced tumorigenesis. , 2008, Cancer research.

[43]  A. Gobert,et al.  Human Microbiota-Secreted Factors Inhibit Shiga Toxin Synthesis by Enterohemorrhagic Escherichia coli O157:H7 , 2008, Infection and Immunity.

[44]  L. Hale,et al.  Helicobacter typhlonius and Helicobacter rodentium differentially affect the severity of colon inflammation and inflammation-associated neoplasia in IL10-deficient mice. , 2008, Comparative medicine.

[45]  S. Lightfoot,et al.  Enterococcus faecalis induces aneuploidy and tetraploidy in colonic epithelial cells through a bystander effect. , 2008, Cancer research.

[46]  Gérard Eberl,et al.  Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis , 2008, Nature.

[47]  B. Roe,et al.  A core gut microbiome in obese and lean twins , 2008, Nature.

[48]  R Balfour Sartor,et al.  Specific microbiota direct the differentiation of IL-17-producing T-helper cells in the mucosa of the small intestine. , 2008, Cell host & microbe.

[49]  G. Tannock Molecular analysis of the intestinal microflora in IBD , 2008, Mucosal Immunology.

[50]  R. Medzhitov,et al.  Innate immune recognition of the indigenous microbial flora , 2008, Mucosal Immunology.

[51]  Shizuo Akira,et al.  Potential link between the immune system and metabolism of nucleic acids. , 2008, Current opinion in immunology.

[52]  R. Ley,et al.  Innate immunity and intestinal microbiota in the development of Type 1 diabetes , 2008, Nature.

[53]  M. Caligiuri,et al.  DNA hypermethylation and epigenetic silencing of the tumor suppressor gene, SLC5A8, in acute myeloid leukemia with the MLL partial tandem duplication. , 2008, Blood.

[54]  M. Kamm,et al.  Dynamics of the Mucosa-Associated Flora in Ulcerative Colitis Patients during Remission and Clinical Relapse , 2008, Journal of Clinical Microbiology.

[55]  J. Fox,et al.  Sex Hormone Influence on Hepatitis in Young Male A/JCr Mice Infected with Helicobacter hepaticus , 2008, Infection and Immunity.

[56]  C. Plass,et al.  Frequently methylated tumor suppressor genes in head and neck squamous cell carcinoma. , 2008, Cancer research.

[57]  Judy H. Cho,et al.  The genetics and immunopathogenesis of inflammatory bowel disease , 2008, Nature Reviews Immunology.

[58]  S. Mazmanian,et al.  A microbial symbiosis factor prevents intestinal inflammatory disease , 2008, Nature.

[59]  Quan P. Ly,et al.  Silencing of the Candidate Tumor Suppressor Gene Solute Carrier Family 5 Member 8 (SLC5A8) in Human Pancreatic Cancer , 2008, Pancreas.

[60]  L. Fulton,et al.  Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. , 2008, Cell host & microbe.

[61]  Jane J. Sohn,et al.  Helicobacter hepaticus Infection Promotes Colon Tumorigenesis in the BALB/c-Rag2−/−ApcMin/+ Mouse , 2008, Infection and Immunity.

[62]  R. Knight,et al.  Error-correcting barcoded primers for pyrosequencing hundreds of samples in multiplex , 2008, Nature Methods.

[63]  J. Fox,et al.  Helicobacter hepaticus promotes azoxymethane‐initiated colon tumorigenesis in BALB/c‐IL10‐deficient mice , 2008, International journal of cancer.

[64]  Tomohiro Watanabe,et al.  Muramyl dipeptide activation of nucleotide-binding oligomerization domain 2 protects mice from experimental colitis. , 2008, The Journal of clinical investigation.

[65]  P. de Vos,et al.  Isolation and Characterization of Human Intestinal Bacteria Capable of Transforming the Dietary Carcinogen 2-Amino-1-Methyl-6-Phenylimidazo[4,5-b]Pyridine , 2008, Applied and Environmental Microbiology.

[66]  L. Joosten,et al.  Stimulation of TLR2 and TLR4 differentially skews the balance of T cells in a mouse model of arthritis. , 2008, The Journal of clinical investigation.

[67]  R. Xu,et al.  Toll-like receptor-4 promotes the development of colitis-associated colorectal tumors. , 2007, Gastroenterology.

[68]  D. Marchuk,et al.  Neonatal Co‐Infection with Helicobacter Species Markedly Accelerates the Development of Inflammation‐Associated Colonic Neoplasia in IL‐10−/–Mice , 2007, Helicobacter.

[69]  S. Girardin,et al.  Nod1 and Nod2 in innate immunity and human inflammatory disorders. , 2007, Biochemical Society transactions.

[70]  M. Murkovic,et al.  Beta-glucuronidase in human intestinal microbiota is necessary for the colonic genotoxicity of the food-borne carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline in rats. , 2007, Carcinogenesis.

[71]  Tomohiro Watanabe,et al.  NOD2 transgenic mice exhibit enhanced MDP-mediated down-regulation of TLR2 responses and resistance to colitis induction. , 2007, Gastroenterology.

[72]  R. Knight,et al.  The Human Microbiome Project , 2007, Nature.

[73]  C. Cerniglia,et al.  Anaerobic Metabolism of 1-Amino-2-Naphthol-Based Azo Dyes (Sudan Dyes) by Human Intestinal Microflora , 2007, Applied and Environmental Microbiology.

[74]  Wendy S. Garrett,et al.  Communicable Ulcerative Colitis Induced by T-bet Deficiency in the Innate Immune System , 2007, Cell.

[75]  N. Pace,et al.  Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases , 2007, Proceedings of the National Academy of Sciences.

[76]  B. Finlay,et al.  Host-mediated inflammation disrupts the intestinal microbiota and promotes the overgrowth of Enterobacteriaceae. , 2007, Cell host & microbe.

[77]  J. Fox,et al.  Bacterial cytolethal distending toxin promotes the development of dysplasia in a model of microbially induced hepatocarcinogenesis , 2007, Cellular microbiology.

[78]  Markus F Neurath,et al.  An inducible mouse model of colon carcinogenesis for the analysis of sporadic and inflammation-driven tumor progression , 2007, Nature Protocols.

[79]  Susan B. Carpenter,et al.  How important are Toll‐like receptors for antimicrobial responses? , 2007, Cellular microbiology.

[80]  R. Medzhitov,et al.  Regulation of Spontaneous Intestinal Tumorigenesis Through the Adaptor Protein MyD88 , 2007, Science.

[81]  M. Daly,et al.  The role of the Toll receptor pathway in susceptibility to inflammatory bowel diseases , 2007, Genes and Immunity.

[82]  C. Fiorentini,et al.  Cytotoxic Necrotizing Factor 1 Prevents Apoptosis via the AKT/IKK pathway: Role of NF-κB and Bcl-2 , 2007 .

[83]  C. Jobin,et al.  Gnotobiotic IL-10−/−;NF-κBEGFP Mice Reveal the Critical Role of TLR/NF-κB Signaling in Commensal Bacteria-Induced Colitis1 , 2007, The Journal of Immunology.

[84]  T. Wang,et al.  A Distinctive Set of Genes Is Upregulated During the Inflammation-Carcinoma Sequence in Mouse Stomach Infected by Helicobacter felis , 2007, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[85]  Mark M Huycke,et al.  Extracellular superoxide production by Enterococcus faecalis promotes chromosomal instability in mammalian cells. , 2007, Gastroenterology.

[86]  A. Biggeri,et al.  Frequent mutation of Apc gene in rat colon tumors and mucin-depleted foci, preneoplastic lesions in experimental colon carcinogenesis. , 2007, Cancer research.

[87]  Sarah L. Brown,et al.  Myd88-dependent positioning of Ptgs2-expressing stromal cells maintains colonic epithelial proliferation during injury. , 2007, The Journal of clinical investigation.

[88]  D. Rosenberg,et al.  Deoxycholic acid promotes the growth of colonic aberrant crypt foci , 2007, Molecular carcinogenesis.

[89]  E. Mardis,et al.  An obesity-associated gut microbiome with increased capacity for energy harvest , 2006, Nature.

[90]  P. Turnbaugh,et al.  Microbial ecology: Human gut microbes associated with obesity , 2006, Nature.

[91]  M. Geier,et al.  Probiotics, prebiotics and synbiotics: A role in chemoprevention for colorectal cancer? , 2006, Cancer biology & therapy.

[92]  Jessica E. Bolden,et al.  Anticancer activities of histone deacetylase inhibitors , 2006, Nature Reviews Drug Discovery.

[93]  L. Hooper,et al.  Symbiotic Bacteria Direct Expression of an Intestinal Bactericidal Lectin , 2006, Science.

[94]  M. McCarthy,et al.  Metabolic profiling reveals a contribution of gut microbiota to fatty liver phenotype in insulin-resistant mice , 2006, Proceedings of the National Academy of Sciences.

[95]  B. Gulluoglu,et al.  A possible role of Bacteroides fragilis enterotoxin in the aetiology of colorectal cancer. , 2006, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[96]  Ruslan Medzhitov,et al.  Role of toll-like receptors in spontaneous commensal-dependent colitis. , 2006, Immunity.

[97]  P. Nambiar,et al.  Innate immune inflammatory response against enteric bacteria Helicobacter hepaticus induces mammary adenocarcinoma in mice. , 2006, Cancer research.

[98]  M. Pop,et al.  Metagenomic Analysis of the Human Distal Gut Microbiome , 2006, Science.

[99]  W. Wade,et al.  Viable Bacteria Present within Oral Squamous Cell Carcinoma Tissue , 2006, Journal of Clinical Microbiology.

[100]  T. Darville,et al.  Recruitment of BAD by the Chlamydia trachomatis Vacuole Correlates with Host-Cell Survival , 2006, PLoS pathogens.

[101]  P. Treuting,et al.  Helicobacter infection is required for inflammation and colon cancer in SMAD3-deficient mice. , 2006, Cancer research.

[102]  F. Bagnoli,et al.  Helicobacter pylori CagA induces a transition from polarized to invasive phenotypes in MDCK cells. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[103]  P. Rutgeerts,et al.  Colorectal cancer in colonic Crohn's disease--high frequency of DNA-aneuploidy. , 2005, Anticancer research.

[104]  C. Manichanh,et al.  Reduced diversity of faecal microbiota in Crohn’s disease revealed by a metagenomic approach , 2005, Gut.

[105]  F. Bäckhed,et al.  Obesity alters gut microbial ecology. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[106]  E. Purdom,et al.  Diversity of the Human Intestinal Microbial Flora , 2005, Science.

[107]  Mark Tsang,et al.  Dual infection with Helicobacter bilis and Helicobacter hepaticus in p-glycoprotein-deficient mdr1a-/- mice results in colitis that progresses to dysplasia. , 2005, The American journal of pathology.

[108]  D. Jewell,et al.  Association between a complex insertion/deletion polymorphism in NOD1 (CARD4) and susceptibility to inflammatory bowel disease. , 2005, Human molecular genetics.

[109]  S. Kimura,et al.  Streptococcus anginosus infection in oral cancer and its infection route. , 2005, Oral diseases.

[110]  M. Abreu,et al.  TLR Signaling in the Gut in Health and Disease1 , 2005, The Journal of Immunology.

[111]  R. Sartor,et al.  Variable phenotypes of enterocolitis in interleukin 10-deficient mice monoassociated with two different commensal bacteria. , 2005, Gastroenterology.

[112]  P. Hylemon,et al.  Diet, anaerobic bacterial metabolism, and colon cancer: a review of the literature. , 2005, Journal of clinical gastroenterology.

[113]  Jason M Doherty,et al.  Activated macrophages are an adaptive element of the colonic epithelial progenitor niche necessary for regenerative responses to injury. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[114]  R. Sartor,et al.  Probiotic therapy of intestinal inflammation and infections , 2005, Current opinion in gastroenterology.

[115]  H. Karch,et al.  Cytolethal Distending Toxin from Shiga Toxin-Producing Escherichia coli O157 Causes Irreversible G2/M Arrest, Inhibition of Proliferation, and Death of Human Endothelial Cells , 2005, Infection and Immunity.

[116]  A. Forbes,et al.  Cancer surveillance in longstanding ulcerative colitis: endoscopic appearances help predict cancer risk , 2004, Gut.

[117]  J. Goedert,et al.  Chlamydia pneumoniae Infection and Risk for Lung Cancer , 2004, Cancer Epidemiology, Biomarkers & Prevention.

[118]  M. Gerlic,et al.  Mycoplasma fermentans inhibits tumor necrosis factor α-induced apoptosis in the human myelomonocytic U937 cell line , 2004, Cell Death and Differentiation.

[119]  C. Hart,et al.  Enhanced Escherichia coli adherence and invasion in Crohn's disease and colon cancer. , 2004, Gastroenterology.

[120]  R. Salem,et al.  Association of Streptococcus bovis bacteremia with colonic neoplasia and extracolonic malignancy. , 2004, Archives of surgery.

[121]  Y. Tachimori,et al.  Frequent and preferential infection of Treponema denticola, Streptococcus mitis, and Streptococcus anginosus in esophageal cancers , 2004, Cancer science.

[122]  T. Azuma,et al.  Meta-analysis of the relationship between CagA seropositivity and gastric cancer. , 2004, Gastroenterology.

[123]  A. Tarnawski,et al.  Deoxycholic acid activates beta-catenin signaling pathway and increases colon cell cancer growth and invasiveness. , 2004, Molecular biology of the cell.

[124]  J. Hampe,et al.  Reduction in diversity of the colonic mucosa associated bacterial microflora in patients with active inflammatory bowel disease , 2004, Gut.

[125]  J. Galán,et al.  Salmonella typhi encodes a functional cytolethal distending toxin that is delivered into host cells by a bacterial-internalization pathway. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[126]  T. Geijtenbeek,et al.  Self- and nonself-recognition by C-type lectins on dendritic cells. , 2004, Annual review of immunology.

[127]  E. Riboli,et al.  Diet and cancer — the European Prospective Investigation into Cancer and Nutrition , 2004, Nature Reviews Cancer.

[128]  L. Hooper,et al.  Bacterial contributions to mammalian gut development. , 2004, Trends in microbiology.

[129]  G. Häcker,et al.  Protection against CD95-Induced Apoptosis by Chlamydial Infection at a Mitochondrial Step , 2004, Infection and Immunity.

[130]  Mark M Huycke,et al.  Bacteria-Induced Intestinal Cancer in Mice with Disrupted Gpx1 and Gpx2 Genes , 2004, Cancer Research.

[131]  X. Tu,et al.  Enteropathogenic and enterohaemorrhagic Escherichia coli deliver a novel effector called Cif, which blocks cell cycle G2/M transition , 2003, Molecular microbiology.

[132]  M. Kundi,et al.  Prevention of heterocyclic amine-induced DNA damage in colon and liver of rats by different lactobacillus strains. , 2003, Carcinogenesis.

[133]  P. Dolara,et al.  Mucin-depleted foci (MDF) in the colon of rats treated with azoxymethane (AOM) are useful biomarkers for colon carcinogenesis. , 2003, Carcinogenesis.

[134]  J. Fox,et al.  CD4(+)CD25(+) regulatory lymphocytes require interleukin 10 to interrupt colon carcinogenesis in mice. , 2003, Cancer research.

[135]  B. Kocazeybek Chronic Chlamydophila pneumoniae infection in lung cancer, a risk factor: a case-control study. , 2003, Journal of medical microbiology.

[136]  R. Medzhitov,et al.  Recognition of microbial infection by Toll-like receptors. , 2003, Current opinion in immunology.

[137]  K. Barrett,et al.  Live probiotics protect intestinal epithelial cells from the effects of infection with enteroinvasive Escherichia coli (EIEC) , 2003, Gut.

[138]  M. Terada,et al.  Different frequencies of Streptococcus anginosus infection in oral cancer and esophageal cancer , 2003, Cancer science.

[139]  P. Dolara,et al.  Identification of mucin-depleted foci in the unsectioned colon of azoxymethane-treated rats: correlation with carcinogenesis. , 2003, Cancer research.

[140]  Jeffrey I. Gordon,et al.  Angiogenins: a new class of microbicidal proteins involved in innate immunity , 2003, Nature Immunology.

[141]  J. Fox,et al.  CD4+ CD25+ regulatory T lymphocytes inhibit microbially induced colon cancer in Rag2-deficient mice. , 2003, The American journal of pathology.

[142]  E. Levy,et al.  Butyrate induced Caco-2 cell apoptosis is mediated via the mitochondrial pathway , 2003, Gut.

[143]  P. Boquet,et al.  CNF1 Exploits the Ubiquitin-Proteasome Machinery to Restrict Rho GTPase Activation for Bacterial Host Cell Invasion , 2002, Cell.

[144]  Jeffrey I. Gordon,et al.  Developmental regulation of intestinal angiogenesis by indigenous microbes via Paneth cells , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[145]  A. Povey,et al.  Total N-nitroso compounds and their precursors in hot dogs and in the gastrointestinal tract and feces of rats and mice: possible etiologic agents for colon cancer. , 2002, The Journal of nutrition.

[146]  J. Pimenta,et al.  Infectious endocarditis from Streptococcus bovis associated with colonic carcinoma: case report and literature review. , 2002, Arquivos de gastroenterologia.

[147]  V. Lievin-Le Moal,et al.  Lactobacillus acidophilus (strain LB) from the resident adult human gastrointestinal microflora exerts activity against brush border damage promoted by a diarrhoeagenic Escherichia coli in human enterocyte-like cells , 2002, Gut.

[148]  T. Warner,et al.  Enterococcus faecalis induces inflammatory bowel disease in interleukin-10 knockout mice. , 2002, The American journal of pathology.

[149]  Lillian Maggio-Price,et al.  Helicobacter bilis infection accelerates and H. hepaticus infection delays the development of colitis in multiple drug resistance-deficient (mdr1a-/-) mice. , 2002, The American journal of pathology.

[150]  T. Meyer,et al.  Epithelial Cells Infected with Chlamydophila pneumoniae (Chlamydia pneumoniae) Are Resistant to Apoptosis , 2001, Infection and Immunity.

[151]  J. Nougayrède,et al.  Type III Secretion-Dependent Cell Cycle Block Caused in HeLa Cells by Enteropathogenic Escherichia coliO103 , 2001, Infection and Immunity.

[152]  I. Wistuba,et al.  Epidemiology and Molecular Pathology of Gallbladder Cancer , 2001, CA: a cancer journal for clinicians.

[153]  C. Montalbán,et al.  Regression of gastric high grade mucosa associated lymphoid tissue (MALT) lymphoma after Helicobacter pylori eradication , 2001, Gut.

[154]  S. Rabot,et al.  Intestinal microflora plays a crucial role in the genotoxicity of the cooked food mutagen 2-amino-3-methylimidazo [4,5-f]quinoline. , 2001, Carcinogenesis.

[155]  G. Lawson,et al.  Lawsonia intracellularis: getting inside the pathogenesis of proliferative enteropathy. , 2001, Veterinary microbiology.

[156]  H. Sidhu,et al.  Rapid reversal of hyperoxaluria in a rat model after probiotic administration of Oxalobacter formigenes. , 2001, The Journal of urology.

[157]  B. Steen,et al.  An association between chronic infection with Chlamydia pneumoniae and lung cancer. A prospective 2‐year study Note , 2001, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[158]  S. Rabot,et al.  Impact of bacteria in dairy products and of the intestinal microflora on the genotoxic and carcinogenic effects of heterocyclic aromatic amines. , 2001, Mutation research.

[159]  T. Kosaka,et al.  Bacterial infection promotes colon tumorigenesis in Apc(Min/+) mice. , 2001, The Journal of infectious diseases.

[160]  Mourad Sahbatou,et al.  Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease , 2001, Nature.

[161]  Judy H. Cho,et al.  A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease , 2001, Nature.

[162]  J. Gordon,et al.  Commensal Host-Bacterial Relationships in the Gut , 2001, Science.

[163]  D. Schauer,et al.  Molecular pathogenesis of Citrobacter rodentium and transmissible murine colonic hyperplasia. , 2001, Microbes and infection.

[164]  K. Abrams,et al.  The risk of colorectal cancer in ulcerative colitis: a meta-analysis , 2001, Gut.

[165]  J. Gordon,et al.  Molecular analysis of commensal host-microbial relationships in the intestine. , 2001, Science.

[166]  J. Galmiche,et al.  Butyrate inhibits inflammatory responses through NFkappaB inhibition: implications for Crohn's disease. , 2000, Gut.

[167]  Harbans Singh,et al.  Carcinoma of the Gallbladder—Is It a Sequel of Typhoid? , 2000, Digestive Diseases and Sciences.

[168]  F. Gossé,et al.  Promotion of intestinal carcinogenesis by Streptococcus bovis. , 2000, Carcinogenesis.

[169]  P. Garg,et al.  Typhoid carriers among patients with gallstones are at increased risk for carcinoma of the gallbladder , 2000, American Journal of Gastroenterology.

[170]  S. Falkow,et al.  Altered states: involvement of phosphorylated CagA in the induction of host cellular growth changes by Helicobacter pylori. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[171]  Shien Tsai,et al.  Mycoplasmal Infections Prevent Apoptosis and Induce Malignant Transformation of Interleukin-3-Dependent 32D Hematopoietic Cells , 1999, Molecular and Cellular Biology.

[172]  É. Oswald,et al.  The bacterial cytolethal distending toxin (CDT) triggers a G2 cell cycle checkpoint in mammalian cells without preliminary induction of DNA strand breaks , 1999, Oncogene.

[173]  M. Blaser,et al.  Role of Helicobacter pylori cagA+ strains and specific host immune responses on the development of premalignant and malignant lesions in the gastric cardia , 1999, International journal of cancer.

[174]  C. Dehio,et al.  Bartonella as emerging pathogens. , 1999, Trends in microbiology.

[175]  R. Sartor,et al.  Resident Enteric Bacteria Are Necessary for Development of Spontaneous Colitis and Immune System Activation in Interleukin-10-Deficient Mice , 1998, Infection and Immunity.

[176]  H. Nagai,et al.  Helicobacter pylori infection induces gastric cancer in mongolian gerbils. , 1998, Gastroenterology.

[177]  C. Janeway,et al.  MyD88 is an adaptor protein in the hToll/IL-1 receptor family signaling pathways. , 1998, Molecular cell.

[178]  Y. Nakanishi,et al.  Presence of Streptococcus anginosus DNA in esophageal cancer, dysplasia of esophagus, and gastric cancer. , 1998, Cancer research.

[179]  C. Fiorentini,et al.  Toxin-induced activation of Rho GTP-binding protein increases Bcl-2 expression and influences mitochondrial homeostasis. , 1998, Experimental cell research.

[180]  B. Chauffert,et al.  Cancer cell sensitization to Fas-mediated apoptosis by sodium butyrate , 1998, Cell Death and Differentiation.

[181]  I. Rowland,et al.  Effect of Bifidobacterium longum and inulin on gut bacterial metabolism and carcinogen-induced aberrant crypt foci in rats. , 1998, Carcinogenesis.

[182]  É. Oswald,et al.  Escherichia coli cytolethal distending toxin blocks the HeLa cell cycle at the G2/M transition by preventing cdc2 protein kinase dephosphorylation and activation , 1997, Infection and immunity.

[183]  J. Fox,et al.  Helicobacter mustelae-associated gastric MALT lymphoma in ferrets. , 1997, The American journal of pathology.

[184]  L. Augenlicht,et al.  Short-chain fatty acid-initiated cell cycle arrest and apoptosis of colonic epithelial cells is linked to mitochondrial function. , 1997, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[185]  J. Shih,et al.  High-Level Expression of H-ras and c-myc Oncogenes in Mycoplasma-Mediated Malignant Cell Transformation , 1997, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[186]  A. Moser,et al.  Intestinal neoplasia in the ApcMin mouse: independence from the microbial and natural killer (beige locus) status. , 1997, Cancer research.

[187]  S A Bingham,et al.  Does increased endogenous formation of N-nitroso compounds in the human colon explain the association between red meat and colon cancer? , 1996, Carcinogenesis.

[188]  J. Shih,et al.  Mycoplasmas and oncogenesis: persistent infection and multistage malignant transformation. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[189]  B. Marshall,et al.  The 1995 Albert Lasker Medical Research Award. Helicobacter pylori. The etiologic agent for peptic ulcer. , 1995, JAMA.

[190]  G. Paumgartner,et al.  Unconjugated secondary bile acids in the serum of patients with colorectal adenomas. , 1995, Gut.

[191]  D. Hicks,et al.  Apoptosis in colorectal tumour cells: Induction by the short chain fatty acids butyrate, propionate and acetate and by the bile salt deoxycholate , 1995, International journal of cancer.

[192]  M. Dimopoulos,et al.  Regression of gastric lymphoma of mucosa-associated lymphoid tissue with antibiotic therapy for Helicobacter pylori. , 1994, Gastroenterology.

[193]  R. Hammer,et al.  The germfree state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic rats , 1994, The Journal of experimental medicine.

[194]  J M Ward,et al.  Chronic active hepatitis and associated liver tumors in mice caused by a persistent bacterial infection with a novel Helicobacter species. , 1994, Journal of the National Cancer Institute.

[195]  M. Hill,et al.  Cancer mortality in chronic typhoid and paratyphoid carriers , 1994, The Lancet.

[196]  T. C. Diss,et al.  Regression of primary low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue type after eradication of Helicobacter pylori , 1993, The Lancet.

[197]  Bandaru S. Reddy,et al.  Inhibitory effect of Bifidobacterium longum on colon, mammary, and liver carcinogenesis induced by 2-amino-3-methylimidazo[4,5-f]quinoline, a food mutagen. , 1993, Cancer research.

[198]  M. Kimmey,et al.  DNA aneuploidy in colonic biopsies predicts future development of dysplasia in ulcerative colitis. , 1992, Gastroenterology.

[199]  M. Sugai,et al.  Bacterial ADP-ribosyltransferase with a substrate specificity of the rho protein disassembles the Golgi apparatus in Vero cells and mimics the action of brefeldin A. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[200]  K. Kinzler,et al.  Corrections and Clarifications: Multiple Intestinal Neoplasia Caused By a Mutation in the Murine Homolog of the APC Gene , 1992, Science.

[201]  A. C. Murphy,et al.  Pasteurella multocida toxin is a potent inducer of anchorage-independent cell growth. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[202]  F. Borchard,et al.  DNA aneuploidy in Crohn's disease and ulcerative colitis: results of a comparative flow cytometric study. , 1992, Gut.

[203]  K. Matsumoto,et al.  Epidermal cell differentiation inhibitor ADP-ribosylates small GTP-binding proteins and induces hyperplasia of epidermis. , 1992, The Journal of biological chemistry.

[204]  P. Isaacson,et al.  Helicobacter pylori-associated gastritis and primary B-cell gastric lymphoma , 1991, The Lancet.

[205]  K. Lillemoe,et al.  The triad of Streptococcus bovis bacteremia, colonic pathology, and liver disease. , 1990, Annals of surgery.

[206]  D. Kingston,et al.  Metabolism of dietary genotoxins by the human colonic microflora; the fecapentaenes and heterocyclic amines. , 1990, Mutation research.

[207]  H. Pitot,et al.  A dominant mutation that predisposes to multiple intestinal neoplasia in the mouse. , 1990, Science.

[208]  S. Miller,et al.  Bacteremia with Streptococcus bovis and Streptococcus salivarius: clinical correlates of more accurate identification of isolates , 1989, Journal of clinical microbiology.

[209]  B. Goldin,et al.  Alterations of the intestinal microflora by diet, oral antibiotics, and Lactobacillus: decreased production of free amines from aromatic nitro compounds, azo dyes, and glucuronides. , 1984, Journal of the National Cancer Institute.

[210]  B. Marshall,et al.  UNIDENTIFIED CURVED BACILLI IN THE STOMACH OF PATIENTS WITH GASTRITIS AND PEPTIC ULCERATION , 1984, The Lancet.

[211]  J. Dwyer,et al.  Effect of diet and Lactobacillus acidophilus supplements on human fecal bacterial enzymes. , 1980, Journal of the National Cancer Institute.

[212]  J. Marr,et al.  ASSOCIATION BETWEEN HEPATOBILIARY CANCER AND TYPHOID CARRIER STATE , 1979, The Lancet.

[213]  S. Barthold,et al.  Morphogenesis of early 1, 2-dimethylhydrazine-induced lesions and latent period reduction of colon carcinogenesis in mice by a variant of Citrobacter freundii. , 1977, Cancer research.

[214]  E. Fiala Investigations into the metabolism and mode of action of the colon carcinogens 1,2‐dimethylhydrazine and azoxymethane , 1977, Cancer.

[215]  S. Edberg,et al.  Association of Streptococcus bovis with carcinoma of the colon. , 1977, The New England journal of medicine.

[216]  E. Wynder,et al.  Promoting effect of bile acids in colon carcinogenesis in germ-free and conventional F344 rats. , 1977, Cancer research.

[217]  E. Wynder,et al.  Metabolic epidemiology of colon cancer: Fecal bile acids and neutral sterols in colon cancer patients and patients with adenomatous polyps , 1977, Cancer.

[218]  J. Weisburger Colon carcinogens: Their metabolism and mode of action , 1971, Cancer.

[219]  G. Laqueur,et al.  Tumor induction in germfree rats with methylazoxymethanol (MAM) and synthetic MAM acetate. , 1967, Journal of the National Cancer Institute.

[220]  Barber Ah Gumm of the thyroid. , 1947 .

[221]  J. Stockman,et al.  Metabolic Syndrome and Altered Gut Microbiota in Mice Lacking Toll-Like Receptor 5 , 2012 .

[222]  A. Chervonsky,et al.  Influence of microbial environment on autoimmunity , 2010, Nature Immunology.

[223]  Mathieu Lemire,et al.  Common variants in the NLRP3 region contribute to Crohn's disease susceptibility , 2009, Nature Genetics.

[224]  A. Neish,et al.  REVIEWS IN BASIC AND CLINICAL GASTROENTEROLOGY Microbes in Gastrointestinal Health and Disease , 2009 .

[225]  A. Sartorelli,et al.  Hyperinduction of Wnt activity: a new paradigm for the treatment of colorectal cancer? , 2008, Oncology research.

[226]  Christopher G. Mathew,et al.  New links to the pathogenesis of Crohn disease provided by genome-wide association scans , 2008, Nature Reviews Genetics.

[227]  A. Miyoshi,et al.  Oral administration of a catalase-producing Lactococcus lactis can prevent a chemically induced colon cancer in mice. , 2008, Journal of medical microbiology.

[228]  C. Jobin,et al.  Gnotobiotic IL-10-/-;NF-kappa B(EGFP) mice reveal the critical role of TLR/NF-kappa B signaling in commensal bacteria-induced colitis. , 2007, Journal of immunology.

[229]  C. Fiorentini,et al.  Cytotoxic necrotizing factor 1 prevents apoptosis via the Akt/IkappaB kinase pathway: role of nuclear factor-kappaB and Bcl-2. , 2007, Molecular biology of the cell.

[230]  Philippe Letonturier,et al.  [Risk factors for colorectal cancer]. , 2005, Presse medicale.

[231]  J. Gordon,et al.  How host-microbial interactions shape the nutrient environment of the mammalian intestine. , 2002, Annual review of nutrition.

[232]  A. Grigoriadis,et al.  Pasteurella multocida toxin: the mitogenic toxin that stimulates signalling cascades to regulate growth and differentiation. , 2001, International journal of medical microbiology : IJMM.

[233]  D. Kim,et al.  Intestinal bacterial beta-glucuronidase activity of patients with colon cancer. , 2001, Archives of pharmacal research.

[234]  C. Weghorst,et al.  Lack of p53 and ras mutations in Helicobacter hepaticus-induced liver tumors in A/JCr mice. , 1997, Carcinogenesis.

[235]  A. Hayday,et al.  T cell receptor-alpha beta-deficient mice fail to develop colitis in the absence of a microbial environment. , 1997, The American journal of pathology.

[236]  I. Rowland,et al.  Lactobacillus- and bifidobacterium-mediated antigenotoxicity in the colon of rats. , 1996, Nutrition and cancer.

[237]  W. Scheppach,et al.  Effects of short chain fatty acids on gut morphology and function. , 1994, Gut.

[238]  G. Paumgartner,et al.  Increased serum deoxycholic acid levels in men with colorectal adenomas. , 1993, Gastroenterology.

[239]  P. Schmezer,et al.  Antigenotoxic properties of lactic acid bacteria in vivo in the gastrointestinal tract of rats. , 1993, Nutrition and cancer.

[240]  C. Cerniglia,et al.  The reduction of azo dyes by the intestinal microflora. , 1992, Critical reviews in microbiology.

[241]  M. C. Archer Mechanisms of action of N-nitroso compounds. , 1989, Cancer surveys.

[242]  Archer Mc Mechanisms of action of N-nitroso compounds. , 1989, Cancer surveys.

[243]  M. Yamamoto,et al.  Effect of beta-glucuronidase inhibitor on azoxymethane-induced colonic carcinogenesis in rats. , 1982, Cancer research.