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1.
ILAR J ; 56(2): 179-91, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26323628

RESUMO

The intestinal microbiota has long been known to play an important role in the maintenance of health. In addition, alterations of the intestinal microbiota have recently been associated with a range of immune-mediated and metabolic disorders. Characterizing the composition and functionality of the intestinal microbiota, unravelling relevant microbe-host interactions, and identifying disease-relevant microbes are therefore currently of major interest in scientific and medical communities. Experimental animal models for the respective diseases of interest are pivotal in order to address functional questions on microbe-host interaction and to clarify the clinical relevance of microbiome alterations associated with disease initiation and development. This review presents an overview of the outcomes of highly sophisticated experimental studies on microbe-host interaction in animal models of inflammatory diseases, with a focus on inflammatory bowel disease (IBD). We will address the advantages and drawbacks of analyzing microbe-host interaction in complex colonized animal models compared with gnotobiotic animal models using monoassociation, simplified microbial consortia (SMC), or microbial humanization.


Assuntos
Microbioma Gastrointestinal/fisiologia , Animais , Modelos Animais de Doenças , Microbioma Gastrointestinal/genética , Vida Livre de Germes/genética , Vida Livre de Germes/fisiologia , Interações Hospedeiro-Patógeno , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/microbiologia
2.
Artigo em Alemão | MEDLINE | ID: mdl-25566836

RESUMO

Recent scientific results underline the importance of the intestinal microbiome, the totality of all intestinal microbes and their genes, for the health of the host organism. The intestinal microbiome can therefore be considered as a kind of "external organ". It has been shown that the intestinal microbiota is a complex and dynamic ecosystem that influences host immunity and metabolism beyond the intestine. The composition and functionality of the intestinal microbiota is of major importance for the development and maintenance of intestinal functions. Inflammatory bowel diseases (IBD) are characterized by dysregulated interactions between the host and its microbiota.The present contribution summarizes current knowledge of the composition and development of the intestinal microbiome and gives an overview of the bidirectional interaction between host and microbiota. The contribution informs about insights regarding the role of the intestinal microbiota in IBD and finally discusses the protective potential of microbial therapies in the context of IBD.


Assuntos
Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/microbiologia , Intestinos/imunologia , Intestinos/microbiologia , Microbiota/imunologia , Humanos , Modelos Biológicos
3.
Inflamm Bowel Dis ; 15(11): 1721-36, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19639558

RESUMO

BACKGROUND: The interleukin 10 knockout mouse (IL10-KO) is a model of human inflammatory bowel disease (IBD) used to study host microbial interactions and the action of potential therapeutics. Using Affymetrix data analysis, important signaling pathways and transcription factors relevant to gut inflammation and antiinflammatory probiotics were identified. METHODS: Affymetrix microarray analysis on both wildtype (WT) and IL10-KO mice orally administered with and without the probiotic VSL#3 was performed and the results validated by real-time polymerase chain reaction (PCR), immunocytochemistry, proteomics, and histopathology. Changes in metabolically active bacteria were assessed with denaturing gradient gel electrophoresis (DGGE). RESULTS: Inflammation in IL10-KO mice was characterized by differential regulation of inflammatory, nuclear receptor, lipid, and xenobiotic signaling pathways. Probiotic intervention resulted in downregulation of CXCL9 (fold change [FC] = -3.98, false discovery rate [FDR] = 0.019), CXCL10 (FC = -4.83, FDR = 0.0008), CCL5 (FC = -3.47, FDR = 0.017), T-cell activation (Itgal [FC = -4.72, FDR = 0.00009], Itgae [FC = -2.54 FDR = 0.0044]) and the autophagy gene IRGM (FC = -1.94, FDR = 0.01), a recently identified susceptibility gene in human IBD. Consistent with a marked reduction in integrins, probiotic treatment decreased the number of CCL5+ CD3+ double-positive T cells and upregulated galectin2, which triggers apoptosis of activated T cells. Importantly, genes associated with lipid and PPAR signaling (PPARalpha [FC = 2.36, FDR = 0.043], PPARGC1alpha [FC = 2.58, FDR = 0.016], Nr1d2 [FC = 3.11, FDR = 0.0067]) were also upregulated. Altered microbial diversity was noted in probiotic-treated mice. CONCLUSIONS: Bioinformatics analysis revealed important immune response, phagocytic and inflammatory pathways dominated by elevation of T-helper cell 1 type (TH1) transcription factors in IL10-KO mice. Probiotic intervention resulted in a site-specific reduction of these pathways but importantly upregulated PPAR, xenobiotic, and lipid signaling genes, potential antagonists of NF-kappaB inflammatory pathways.


Assuntos
Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/terapia , Metabolismo dos Lipídeos/imunologia , Probióticos/farmacologia , Transdução de Sinais/imunologia , Xenobióticos/farmacologia , Animais , Ceco/fisiologia , Quimiocina CCL5/metabolismo , Colo/fisiologia , Modelos Animais de Doenças , Doenças Inflamatórias Intestinais/genética , Interleucina-10/genética , Camundongos , Camundongos Knockout , Análise de Sequência com Séries de Oligonucleotídeos , Fagocitose/imunologia , Proteômica , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Streptococcus thermophilus
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