Gut microbiota profile and immune responses in piglet and mice models of inflammatory bowel disease: The impact of antepartum use of antibiotics, prebiotics and probiotics

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Date
2016-09, 2016-04, 2015-11, 2014-10
Authors
Munyaka, Peris Mumbi
Journal Title
Journal ISSN
Volume Title
Publisher
Journal of Basic Microbiology
Frontiers in Microbiology
PLoS One
Frontiers in Pediatrics
Abstract
A major challenge facing scientists is to find a full understanding of the factors behind inflammatory bowel disease’ [IBD; including ulcerative colitis (UC) and Crohn’s disease (CD)] pathogenesis and optimal treatment. This is demonstrated by the fact that despite many years of research, IBD is still an idiopathic disease whose cure is far from reach. IBD is currently recognized as a global burden and could be due to genetic, environmental, microbiota or immune-related factors. The gut microbiota co-evolve with the host and therefore play an important role in the development and maturation of the immune system. Hence, changes in the composition, distribution and functional activities of the gut microbiota might predispose to IBD. In five studies, the role of adherent invasive Escherichia coli (AIEC) strain UM146 and antepartum antibiotics on gut microbiota dysbiosis and susceptibility to colitis, and therapeutic impact of prebiotics (resistant starch; RS) and probiotics (E. coli UM 2 & 7), in mice and pig models of colitis were investigated. Weaner pigs received 1 % degraded carrageenan gum (CG) for 21 days and were inoculated with AIEC on day 8. CG-induced colitis caused bacterial dysbiosis similar to observations in IBD patients; however, AIEC did not show clear impacts. In the second study, weaner pigs received 1 % CG for 21 days and RS and the E. coli probiotics therapies were administered from day 8 until end of the study. Inclusion of RS and E. coli probiotics showed minimal effects in modulation of bacterial dysbiosis and inflammation. The third study investigated protective and therapeutic effects of RS in a 40-day experiment. Inclusion of RS modulated inflammation, histological damage and bacterial dysbiosis. The fourth study investigated impact of 5 % dextran sodium sulphate (DSS)-induced colitis in mice for 5 days; DSS caused inflammation and bacterial dysbiosis. In the last study, pregnant mice were injected with antibiotic cefazolin (160 mg/kg bw) 6 days before due date and the offspring were exposed to 4 % DSS-induced colitis at 7 weeks of age. Antepartum antibiotics influenced offspring intestinal bacterial colonization predisposing them to colitis later in life. Overall, this work demonstrates the critical role of DSS/CG-induced colitis and antepartum antibiotics in disrupting existing or initial composition of gut microbiota, and the role this disruption might play in the development of IBD. Also, the work highlights significant role of RS in IBD treatment and hold implications and potential for advancement in the management of IBD.
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Keywords
Inflammatory bowel disease, Microbiota, Inflammation, Crohn's disease, Pig model, Mice model, Dysbiosis, Dextran sulphate sodium, Degraded carrageenan gum, Ulcerative colitis, Prebiotics, Probiotics, Antepartum antibiotics
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