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Title: Describing the gut microbiome and metabolomic changes in bile acid diarrhoea (BAD)
Author: Sagar, Nidhi
ISNI:       0000 0004 7227 5978
Awarding Body: University of Warwick
Current Institution: University of Warwick
Date of Award: 2017
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The diagnosis of BAD is often missed or misdiagnosed for IBS-D as these conditions present similarly with chronic diarrhoea. The principal hindrance to diagnosis of BAD is limited access to the diagnostic SeHCAT scan. Mechanisms of aetiology underlying BAD have not been fully elucidated and to date, an alternative biomarker for BAD that is more accessible and patient preferable, has yet to make its way into clinical practice. One of the greatest scientific challenges this decade has been understanding the relationship between the gut microbiome, its functionality and role in human health. BAs are metabolised by the gut microbiota, therefore their role as signalling molecules in regulating intestinal homeostasis is influenced primarily by the gut commensals. This thesis is the first study to profile the gut microbiome in BAD and investigate the mechanisms of how bacterial metabolic products may influence the development of disease. This was achieved by conducting 16S ribosomal RNA gene analysis, the most important target of study in bacterial ecology. Bacterial metabolites (SCFAs and VOCs) and BAs were measured using gas and liquid chromatography, mass and ion mobility spectrometry. The results indicate intestinal dysbiosis with reduced bacterial diversity in patients with BAD. A statistically significantly greater total concentration of SCFAs with increases in the concentrations of acetate and propionate were observed in BAD compared to IBS-D. A statistically significant increase in the concentrations of faecal primary BAs and serum CDCA was observed in BAD compared to IBS-D. Separation of VOC profiles was evident between the BAD, IBS-D and HC groups but greatest discrimination was between the IBS-D and HC cohorts. In conclusion, intestinal dysbiosis with altered fermentation and resultant BA dysmetabolism were observed. The metabolic output of the microbiota rather than abundance of specific bacterial taxa appears to be more important in the aetiology of BAD.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: RC Internal medicine