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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

Cellular & Molecular Immunology volume 8, pages 110–120 (2011)Cite this article

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.

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Acknowledgements

This study was supported by grants from the Czech Science Foundation (nos. 303/08/0367, 303/09/0449, 310/07/014, 305/08/0535, 310/09/1640 and 310/08/H077), the Grant Agency of the Academy of Sciences of the Czech Republic (nos. IAA500200910, IAA500200710, KJB500200904, IAA500200917 and A500200709), the Ministry of Education, Youth and Sports of the Czech Republic (nos. 2B06053, 2B06155 and MSM 0021620812), the Ministry of Health of the Czech Republic (nos. NS/9775-4, NS/10054-3 and NS/10340-3), by EU Project Marie Curie CT 215553, EU Project IPODD consortium (202020) and the Institutional Research Concept AV0Z50200510.

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  1. Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i., Prague, Czech Republic

    Helena Tlaskalová-Hogenová, Renata Štěpánková, Hana Kozáková, Tomáš Hudcovic, Luca Vannucci, Ludmila Tučková, Pavel Rossmann, Tomáš Hrnčíř, Miloslav Kverka, Zuzana Zákostelská, Klára Klimešová, Jaroslava Přibylová, Daniel Sanchez, Petra Fundová, Dana Borovská, Dagmar Šrůtková, Martin Schwarzer & David P Funda

  2. Institute of Dental Research, General Faculty Hospital and 1st Faculty of Medicine, Charles University, Prague, Czech Republic

    Jiřina Bártová

  3. Nose and Throat Department, Ear, Central Military Hospital, Prague, Czech Republic

    Petra Fundová

  4. Institute of Experimental Medicine, Academy of Science of the Czech Republic, Prague, Czech Republic

    Zdeněk Zídek

  5. Institute of Clinical and Experimental Medicine, Prague, Czech Republic

    Pavel Drastich

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  1. Helena Tlaskalová-Hogenová
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Correspondence to Helena Tlaskalová-Hogenová.

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Tlaskalová-Hogenová, H., Štěpánková, R., Kozáková, H. et al. 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. Cell Mol Immunol 8, 110–120 (2011). https://doi.org/10.1038/cmi.2010.67

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