Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.656507
Title: Metabonomic investigations of the mammalian host-gut microbiome interactions in obesity and metabolic diseases
Author: Boulange, Claire
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2013
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Abstract:
Obesity is known to contribute to the risk of developing type 2 diabetes mellitus, non-alcoholic fatty liver diseases, cancer, osteoarthritis and cardiovascular diseases. Obesity results from an imbalance between energy intake and energy expenditure but its aetiology is complex and not completely understood. Genetic and environmental factors, (high calorie diet, lack of physical activity) strongly influence the onset of obesity and metabolic diseases. Modifications of gut microbial-host metabolic interactions by dietary interventions also contribute to obesity and are associated with metabolic disturbances. Noticeably, some obese individuals seem protected from the development of metabolic diseases which highlight individual predispositions to obesity associated metabolic disturbances. It is therefore important to underpin the molecular mechanisms linked to obesity and the role of gut microbiota in the degradation of a healthy phenotype in an appropriate biological model. 1H nuclear magnetic spectroscopy and mass spectrometry analysis were employed to measure the abundant metabolites in C57BL/6 mouse urine, feces, and plasma. Metabolic profiles of mice subjected to dietary interventions were compared using multivariate statistics. Alterations of gut microbial ecosystem by dietary interventions were also assessed by 16s rRNA pyrosequencing of mouse fecal microbiota. When given a high fat diet, the obesity prone and obesity resistant mice showed differences in leucine catabolism and tricarboxylic cycle. This may indicate specific regulations of mitochondrial oxidative pathways during diet induced obesity (DIO), influencing obesity development and metabolic disturbances. Possible roles of gut microbiota in the regulation of mitochondrial oxidative pathways were also envisaged. Gut microbial remodelling by the supplementation of different prebiotic blends (galactosyl-oligosaccharides, fructosyl-oligosaccharides and inulin or galactosyl-oligosaccharides and cow milk oligosaccharides) during a high fat challenge also decreased obesity and low grade inflammation and affect mouse metabolism. Decreased gut bacterial amino acids fermentation by prebiotic supplementation may contribute to the improvement of mouse physiology during DIO.
Supervisor: Dumas, Marc Sponsor: NestleĢ
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.656507  DOI: Not available
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