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
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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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The gut microbiota have an important role in promoting the development, maintenance, and function of the intestinal barrier by increasing IgA production and mucin expression, preventing intestinal epithelial cell apoptosis, inhibiting colonization by enteric pathogens, and promoting physiological immune responses.
“The gut microbiota have an important role in promoting the development, maintenance, and function of the intestinal barrier by increasing IgA production and mucin expression, preventing intestinal epithelial cell apoptosis, inhibiting colonization by enteric pathogens, and promoting physiological immune responses (113, 173, 178).”
From Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome (2013) · cites this paper as [173]
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- Authors
- Tlaskalová-Hogenová, H., Štěpánková, R., Kozáková, H., Hudcovic, T., Vannucci, L., Tučková, L., Rossmann, P., Hrnčíř, T., Kverka, M., Zákostelská, Z., Klimešová, K., Přibylová, J., Bártová, J., Sanchez, D., Fundová, P., Borovská, D., Šrůtková, D., Zídek, Z., Schwarzer, M., Drastich, P., & Funda, D. P.
- Affiliations
- Czech Academy of Sciences (CZ)
- Charles University (CZ)
- Institute of Clinical and Experimental Medicine (CZ)
- Corresponding author
- Tlaskalová-Hogenová, Helena
- ORCID
- Venue
- Cellular & Molecular Immunology
- Published
- 2011-01-31
- Volume
- 8
- Issue
- 2
- Pages
- 110-120
- ISSN
- 1672-7681 (ISSN-L)
- 2042-0226
- PMC
- PMC4003137
- OpenAlex
- W2122921940
- Cited by
- 693
- References
- 171
- Citations by year
- 2026: 21 · 2025: 22 · 2024: 30 · 2023: 43 · 2022: 54 · 2021: 68 · 2020: 54 · 2019: 54 · 2018: 45 · 2017: 58 · 2016: 54 · 2015: 47 · 2014: 51 · 2013: 40 · 2012: 41
- FWCI
- 4.15
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Cellular and Molecular Immunology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- ASEP (submittedVersion, public-domain)
- Funders
- Grantová Agentura České Republiky
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Keywords
- gut microbiota, commensal bacteria, mucosal barrier, inflammatory bowel disease, colorectal cancer, colonic neoplasia, autoimmune diabetes, atherosclerosis, ApoE-deficient mice, mucosal tolerance, germ-free animals, gnotobiotic models, microbiome, probiotics, prebiotics, disease prevention
- MeSH terms
- Animals, Autoimmune Diseases, Disease Models, Animal, Germ-Free Life, Humans, Immunity, Inflammation, Mucous Membrane, Neoplasms, Gastrointestinal Tract, Metagenome
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