The role of microbiota in infectious disease.

The intestine harbors an ecosystem composed of the intestinal mucosa and the commensal microbiota. The microbiota fosters development, aids digestion and protects host cells from pathogens - a function referred to as colonization resistance. Little is known about the molecular basis of colonization resistance and how it can be overcome by enteropathogenic bacteria. Recently, studies on inflammatory bowel diseases and on animal models for enteric infection have provided new insights into colonization resistance. Gut inflammation changes microbiota composition, disrupts colonization resistance and enhances pathogen growth. Thus, some pathogens can benefit from inflammatory defenses. This new paradigm will enable the study of host factors enhancing or inhibiting bacterial growth in health and disease.

[1]  F. Fang,et al.  Co‐regulation of Salmonella enterica genes required for virulence and resistance to antimicrobial peptides by SlyA and PhoP/PhoQ , 2005, Molecular microbiology.

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

[3]  J. Ballard,et al.  Clostridium difficile Toxins: Mechanism of Action and Role in Disease , 2005, Clinical Microbiology Reviews.

[4]  A. McCartney Application of molecular biological methods for studying probiotics and the gut flora , 2002, British Journal of Nutrition.

[5]  B. Stocker,et al.  Roles of motility, chemotaxis, and penetration through and growth in intestinal mucus in the ability of an avirulent strain of Salmonella typhimurium to colonize the large intestine of streptomycin-treated mice , 1988, Infection and immunity.

[6]  H. Gill Probiotics to enhance anti-infective defences in the gastrointestinal tract. , 2003, Best practice & research. Clinical gastroenterology.

[7]  J. Gordon,et al.  A Model of Host-Microbial Interactions in an Open Mammalian Ecosystem , 1996, Science.

[8]  G. Wu,et al.  How to evaluate a gastric submucosal tumour in a patient with haematemesis? , 2005, Gut.

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

[10]  Thomas A. Ficht,et al.  Of Mice, Calves, and Men , 1999 .

[11]  F. Shanahan,et al.  The gut flora as a forgotten organ , 2006, EMBO reports.

[12]  G. Frankel,et al.  Enteropathogenic Escherichia coli: unravelling pathogenesis. , 2005, FEMS microbiology reviews.

[13]  C. Wells,et al.  Ulcerative colitis and Crohn's disease. , 1952, Annals of the Royal College of Surgeons of England.

[14]  B. Stecher,et al.  Comparison of Salmonellaenterica Serovar Typhimurium Colitis in Germfree Mice and Mice Pretreated with Streptomycin , 2005, Infection and Immunity.

[15]  I. Kétyi Feeding by mucin and intestinal growth of some enteric bacterial pathogens. , 1988, Acta microbiologica Hungarica.

[16]  James R. Knight,et al.  Genome sequencing in microfabricated high-density picolitre reactors , 2005, Nature.

[17]  K. Klose The suckling mouse model of cholera. , 2000, Trends in microbiology.

[18]  R. Kingsley,et al.  Of mice, calves, and men. Comparison of the mouse typhoid model with other Salmonella infections. , 1999, Advances in experimental medicine and biology.

[19]  J. Dekker,et al.  Distinct epithelial responses in experimental colitis: implications for ion uptake and mucosal protection. , 2002, American journal of physiology. Gastrointestinal and liver physiology.

[20]  D. Sack,et al.  Improved outcome in shigellosis associated with butyrate induction of an endogenous peptide antibiotic. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

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

[22]  H. Sahl,et al.  The co-evolution of host cationic antimicrobial peptides and microbial resistance , 2006, Nature Reviews Microbiology.

[23]  Joe E Grissom,et al.  Carbon nutrition of Escherichia coli in the mouse intestine. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[24]  G. Tannock Molecular assessment of intestinal microflora. , 2001, The American journal of clinical nutrition.

[25]  M. Dumont,et al.  Stable isotope probing — linking microbial identity to function , 2005, Nature Reviews Microbiology.

[26]  U. Göbel,et al.  Shift Towards Pro-inflammatory Intestinal Bacteria Aggravates Acute Murine Colitis via Toll-like Receptors 2 and 4 , 2007, PloS one.

[27]  B. Finlay,et al.  Citrobacter rodentium translocated intimin receptor (Tir) is an essential virulence factor needed for actin condensation, intestinal colonization and colonic hyperplasia in mice , 2003, Molecular microbiology.

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

[29]  Finkelstein Ra,et al.  Pathogenesis of Experimental Cholera in Infant Rabbits: I. Observations on the Intraintestinal Infection and Experimental Cholera Produced with Cell-Free Products , 1964 .

[30]  R. Ley,et al.  Ecological and Evolutionary Forces Shaping Microbial Diversity in the Human Intestine , 2006, Cell.

[31]  G. Dougan,et al.  Salmonella enterica Serovar Typhimurium Exploits Inflammation to Compete with the Intestinal Microbiota , 2007, PLoS biology.

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

[33]  I. Sasaki,et al.  Identification of genes involved in mucosal defense and inflammation associated with normal enteric bacteria. , 2000, American journal of physiology. Gastrointestinal and liver physiology.

[34]  B. Deplancke,et al.  Microbial modulation of innate defense: goblet cells and the intestinal mucus layer. , 2001, The American journal of clinical nutrition.

[35]  C. Dietrich,et al.  Enhanced expression of MMP‐7 and MMP‐13 in inflammatory bowel disease: A precancerous potential? , 2006, Inflammatory bowel diseases.

[36]  O. Froy Microreview: Regulation of mammalian defensin expression by Toll‐like receptor‐dependent and independent signalling pathways , 2005, Cellular microbiology.

[37]  I. Autenrieth,et al.  Experimental Yersinia enterocolitica infection in rodents: A model for human yersiniosis , 1993, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[38]  M. Bohnhoff,et al.  Effect of Streptomycin on Susceptibility of Intestinal Tract to Experimental Salmonella Infection.∗ , 1954, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[39]  K. McCoy,et al.  Use of axenic animals in studying the adaptation of mammals to their commensal intestinal microbiota. , 2007, Seminars in immunology.

[40]  S. Rosewicz,et al.  Differential expression of matrix metalloproteinases and their tissue inhibitors in colon mucosa of patients with inflammatory bowel disease , 2000, Gut.

[41]  P. L. Stark,et al.  The microbial ecology of the large bowel of breast-fed and formula-fed infants during the first year of life. , 1982, Journal of medical microbiology.

[42]  V. Mai,et al.  Monitoring of Stool Microbiota in Subjects with Diarrhea Indicates Distortions in Composition , 2006, Journal of Clinical Microbiology.

[43]  J. Gordon,et al.  Functional Genomic Studies of the Intestinal Response to a Foodborne Enteropathogen in a Humanized Gnotobiotic Mouse Model* , 2007, Journal of Biological Chemistry.

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

[45]  J. Gordon,et al.  Bacterial Exposure Induces and Activates Matrilysin in Mucosal Epithelial Cells , 2000, The Journal of cell biology.

[46]  S. Hapfelmeier,et al.  A mouse model for S. typhimurium-induced enterocolitis. , 2005, Trends in microbiology.

[47]  A. Phalipon,et al.  A newborn mouse model for the study of intestinal pathogenesis of shigellosis , 2003, Cellular microbiology.

[48]  M. Kagnoff,et al.  Cathelicidin Mediates Innate Intestinal Defense against Colonization with Epithelial Adherent Bacterial Pathogens1 , 2005, The Journal of Immunology.

[49]  J. Costerton,et al.  Microbial flora of the mouse ileum mucous layer and epithelial surface , 1982, Applied and environmental microbiology.

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

[51]  B. Finlay,et al.  Analysis of the Contribution of Salmonella Pathogenicity Islands 1 and 2 to Enteric Disease Progression Using a Novel Bovine Ileal Loop Model and a Murine Model of Infectious Enterocolitis , 2005, Infection and Immunity.

[52]  M. Mann,et al.  Robust Salmonella metabolism limits possibilities for new antimicrobials , 2006, Nature.

[53]  I. Lawrance,et al.  Ulcerative colitis and Crohn's disease: distinctive gene expression profiles and novel susceptibility candidate genes. , 2001, Human molecular genetics.

[54]  P. Sansonetti,et al.  IL-8 Is a Key Chemokine Regulating Neutrophil Recruitment in a New Mouse Model of Shigella-Induced Colitis , 2004, The Journal of Immunology.

[55]  Emma Allen-Vercoe,et al.  Lack of flagella disadvantages Salmonella enterica serovar Enteritidis during the early stages of infection in the rat. , 2003, Journal of medical microbiology.

[56]  C. Thorpe Shiga toxin-producing Escherichia coli infection. , 2004, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[57]  G. Rossi,et al.  Mucosal lymphoid infiltrate dominates colonic pathological changes in murine experimental shigellosis. , 2005, The Journal of infectious diseases.

[58]  M. Albert,et al.  Development of an improved animal model of shigellosis in the adult rabbit by colonic infection with Shigella flexneri 2a , 1995, Infection and immunity.

[59]  T. Ganz Defensins: antimicrobial peptides of innate immunity , 2003, Nature Reviews Immunology.

[60]  R. Finkelstein,et al.  Ability of an avirulent mutant of Vibrio cholerae to colonize in the infant mouse upper bowel , 1981, Infection and immunity.

[61]  L. Bossi,et al.  Differential accumulation of Salmonella[Cu, Zn] superoxide dismutases SodCI and SodCII in intracellular bacteria: correlation with their relative contribution to pathogenicity , 2002, Molecular microbiology.

[62]  Rachel E. Klevit,et al.  Recognition of Antimicrobial Peptides by a Bacterial Sensor Kinase , 2005, Cell.

[63]  R. Gibbons,et al.  Impaired colonization of gnotobiotic and conventional rats by streptomycin-resistant strains of Streptococcus mutans , 1978, Infection and immunity.

[64]  W. Eling,et al.  Apathogenic, intestinal, segmented, filamentous bacteria stimulate the mucosal immune system of mice , 1993, Infection and immunity.

[65]  L. Eckmann,et al.  Innate immune defenses in the intestinal tract , 2007, Current opinion in gastroenterology.

[66]  J. Cummings The large intestine in nutrition and disease. , 1997 .

[67]  D. van der Waaij,et al.  Colonization resistance of the digestive tract in conventional and antibiotic-treated mice. , 1971 .

[68]  U. Sauer,et al.  Getting Closer to the Whole Picture , 2007, Science.

[69]  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.

[70]  Daniel B. DiGiulio,et al.  Development of the Human Infant Intestinal Microbiota , 2007, PLoS biology.

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

[72]  B. Finlay,et al.  Interplay between antibacterial effectors: a macrophage antimicrobial peptide impairs intracellular Salmonella replication. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[73]  C. Sasakawa,et al.  New Animal Model of Shigellosis in the Guinea Pig: Its Usefulness for Protective Efficacy Studies1 , 2007, The Journal of Immunology.

[74]  E. Bambirra,et al.  Intragastric infection of germfree and conventional mice with Salmonella typhimurium. , 1989, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[75]  N. Ganguly,et al.  Role of reactive oxygen species in Salmonella typhimurium-induced enterocyte damage. , 1998, Scandinavian journal of gastroenterology.

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

[77]  Michael B. Eisen,et al.  Rapid quantitative profiling of complex microbial populations , 2006, Nucleic acids research.

[78]  A. Abo,et al.  R-spondin1, a novel intestinotrophic mitogen, ameliorates experimental colitis in mice. , 2007, Gastroenterology.

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

[80]  D. Savage Microbial ecology of the gastrointestinal tract. , 1977, Annual review of microbiology.

[81]  Thomas Lengauer,et al.  Dissection of the Inflammatory Bowel Disease Transcriptome Using Genome-Wide cDNA Microarrays , 2005, PLoS medicine.

[82]  D. Relman,et al.  The role of microbes in Crohn's disease. , 2007, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[83]  R. Freter In vivo and in vitro antagonism of intestinal bacteria against Shigellaflexneri. II. The inhibitory mechanism. , 1962, The Journal of infectious diseases.

[84]  T. Wallis,et al.  Salmonella Pathogenicity Island 2 Influences Both Systemic Salmonellosis andSalmonella-Induced Enteritis in Calves , 2001, Infection and Immunity.

[85]  J. Gordon,et al.  Genomic and Metabolic Studies of the Impact of Probiotics on a Model Gut Symbiont and Host , 2006, PLoS biology.