Robinson, AM and Gondalia, SV and Karpe, AV and Eri, R and Beale, DJ and Morrison, PD and Palombo, EA and Nurgali, K, Fecal microbiota and metabolome in a mouse model of spontaneous chronic colitis: relevance to human inflammatory bowel disease, Inflammatory Bowel Diseases, 22, (12) pp. 2767-2787. ISSN 1078-0998 (2016) [Refereed Article]
Copyright 2016 Crohn’s & Colitis Foundation of America, Inc.
Background: Dysbiosis of the gut microbiota may be involved in the pathogenesis of inflammatory bowel disease (IBD). However, the mechanisms underlying the role of the intestinal microbiome and metabolome in IBD onset and its alteration during active treatment and recovery remain unknown. Animal models of chronic intestinal inflammation with similar microbial and metabolomic profiles would enable investigation of these mechanisms and development of more effective treatments. Recently, the Winnie mouse model of colitis closely representing the clinical symptoms and characteristics of human IBD has been developed. In this study, we have analyzed fecal microbial and metabolomic profiles in Winnie mice and discussed their relevance to human IBD.
Methods: The 16S rRNA gene was sequenced from fecal DNA of Winnie and C57BL/6 mice to define operational taxonomic units at ≥97% similarity threshold. Metabolomic profiling of the same fecal samples was performed by gas chromatography-mass spectrometry.
Results: Composition of the dominant microbiota was disturbed, and prominent differences were evident at all levels of the intestinal microbiome in fecal samples from Winnie mice, similar to observations in patients with IBD. Metabolomic profiling revealed that chronic colitis in Winnie mice upregulated production of metabolites and altered several metabolic pathways, mostly affecting amino acid synthesis and breakdown of monosaccharides to short chain fatty acids.
Conclusions: Significant dysbiosis in the Winnie mouse gut replicates many changes observed in patients with IBD. These results provide justification for the suitability of this model to investigate mechanisms underlying the role of intestinal microbiota and metabolome in the pathophysiology of IBD.
|Item Type:||Refereed Article|
|Keywords:||IBD, proteomics, inflammatory bowel disease, microbiota, metabolome, spontaneous chronic colitis, Winnie mouse model|
|Research Division:||Biological Sciences|
|Research Field:||Genetic Immunology|
|Objective Group:||Clinical Health (Organs, Diseases and Abnormal Conditions)|
|Objective Field:||Digestive System Disorders|
|Author:||Eri, R (Associate Professor Raj Eri)|
|Web of Science® Times Cited:||6|
|Deposited By:||Health Sciences|
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