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Title: Influence of iron supplementation on gut microbiota and the natural history of inflammatory bowel disease
Author: Mahalhal, Awad
ISNI:       0000 0004 6495 8138
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2017
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Inflammatory bowel disease (IBD) is idiopathic in origin and is associated with damaged mucosa which may bleed and result in anaemia. Iron deficiency is common in IBD and has been shown to be involved in the pathogenesis of the anaemia of patients with IBD. Treatment of iron deficiency with oral iron supplementation may intensify inflammation and tissue damage, and there is evidence that iron supplementation induces inflammation both in normal rats and in rodent models of IBD. The intestinal microbiota is considered to play a vital role in the pathogenesis of IBD, and various studies have confirmed the presence of intestinal dysbiosis in IBD patients compared to healthy controls. Furthermore, iron supplementation has been shown to influence microbial diversity. This thesis studies the effect of iron on gut microbial composition in the presence of mucosal inflammation. These aims were addressed using acute and chronic (DSS) murine models of IBD using wild-type C57BL/6 mice receiving diets differing in iron content. Bacterial gDNA was extracted from faeces, and the microbiota composition was determined by sequencing the V4 region of 16S rDNA on the Illumina MiSeq platform. DSS-induced colitis in all treated mice, but a low iron consumption was clinically (body weight (p < 0.001) and histology (p < 0.0001)) more influential on colitis. Whereas, high iron intake was more prominent regarding intestinal microbiota disturbance (reduction in Bacteroidetes and Firmicutes and an increase in Proteobacteria and Actinobacteria). This thesis demonstrates that changes in nutritional luminal iron (100ppm and 400ppm iron) exacerbate colitis and cause dysbiosis in mice with acute or chronic colitis. Iron, therefore, appears to contribute to the dysbiosis which is associated with IBD.
Supervisor: Probert, C. ; Campbell, B. ; Pritchard, D. M. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral