title: The role of gut microbiota (commensal bacteria) and the mucosal barrier in the pathogenesis of inflammatory and autoimmune diseases and cancer: contribution of germ-free and gnotobiotic animal models of human diseases.
abstract: Metagenomic approaches are currently being used to decipher the genome of the microbiota (microbiome), and, in parallel, functional studies are being performed to analyze the effects of the microbiota on the host. Gnotobiological methods are an indispensable tool for studying the consequences of bacterial colonization. Animals used as models of human diseases can be maintained in sterile conditions (isolators used for germ-free rearing) and specifically colonized with defined microbes (including non-cultivable commensal bacteria). The effects of the germ-free state or the effects of colonization on disease initiation and maintenance can be observed in these models. Using this approach we demonstrated direct involvement of components of the microbiota in chronic intestinal inflammation and development of colonic neoplasia (i.e., using models of human inflammatory bowel disease and colorectal carcinoma). In contrast, a protective effect of microbiota colonization was demonstrated for the development of autoimmune diabetes in non-obese diabetic (NOD) mice. Interestingly, the development of atherosclerosis in germ-free apolipoprotein E (ApoE)-deficient mice fed by a standard low-cholesterol diet is accelerated compared with conventionally reared animals. Mucosal induction of tolerance to allergen Bet v1 was not influenced by the presence or absence of microbiota. Identification of components of the microbiota and elucidation of the molecular mechanisms of their action in inducing pathological changes or exerting beneficial, disease-protective activities could aid in our ability to influence the composition of the microbiota and to find bacterial strains and components (e.g., probiotics and prebiotics) whose administration may aid in disease prevention and treatment.
authors.affiliation: Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i., Prague, Czech Republic. tlaskalo@biomed.cas.cz
authors.forename: Helena
authors.initials: H
authors.lastname: Tlaskalová-Hogenová
authors.forename: Renata
authors.initials: R
authors.lastname: Stěpánková
authors.forename: Hana
authors.initials: H
authors.lastname: Kozáková
authors.forename: Tomáš
authors.initials: T
authors.lastname: Hudcovic
authors.forename: Luca
authors.initials: L
authors.lastname: Vannucci
authors.forename: Ludmila
authors.initials: L
authors.lastname: Tučková
authors.forename: Pavel
authors.initials: P
authors.lastname: Rossmann
authors.forename: Tomáš
authors.initials: T
authors.lastname: Hrnčíř
authors.forename: Miloslav
authors.initials: M
authors.lastname: Kverka
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Zákostelská
authors.forename: Klára
authors.initials: K
authors.lastname: Klimešová
authors.forename: Jaroslava
authors.initials: J
authors.lastname: Přibylová
authors.forename: Jiřina
authors.initials: J
authors.lastname: Bártová
authors.forename: Daniel
authors.initials: D
authors.lastname: Sanchez
authors.forename: Petra
authors.initials: P
authors.lastname: Fundová
authors.forename: Dana
authors.initials: D
authors.lastname: Borovská
authors.forename: Dagmar
authors.initials: D
authors.lastname: Srůtková
authors.forename: Zdeněk
authors.initials: Z
authors.lastname: Zídek
authors.forename: Martin
authors.initials: M
authors.lastname: Schwarzer
authors.forename: Pavel
authors.initials: P
authors.lastname: Drastich
authors.forename: David P
authors.initials: DP
authors.lastname: Funda
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology* / Q000382:microbiology; D004195:Disease Models, Animal; D041981:Gastrointestinal Tract / Q000382:microbiology*; D005856:Germ-Free Life; D006801:Humans; D007109:Immunity; D007249:Inflammation / Q000209:etiology* / Q000382:microbiology; D054892:Metagenome / Q000276:immunology*; D009092:Mucous Membrane / Q000276:immunology*; D009369:Neoplasms / Q000209:etiology* / Q000382:microbiology