Dietary Manipulation of Gut Microbiota for Improvement of Metabolic Health

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atmire.migration.oldid4559
dc.contributor.advisorReimer, Raylene
dc.contributor.authorBomhof, Marc
dc.contributor.committeememberShearer, Jane
dc.contributor.committeememberHittel, Dustin
dc.contributor.committeememberChelikani, Prasanth
dc.contributor.committeememberComelli, Elena
dc.date.accessioned2016-07-05T16:42:46Z
dc.date.available2016-07-05T16:42:46Z
dc.date.issued2016
dc.date.submitted2016en
dc.description.abstractBackground: Obesity is a highly complex disease state for which there remains a dearth of effective treatment and prevention strategies. An abundance of research now suggests that gut microbiota plays a role in the pathogenesis of obesity, making it a prime target for obesity management. Objective: This dissertation examines how dietary agents including prebiotics and probiotics, gut microbiota, and host physiology interact to affect metabolic health in obesity. Specifically, the objectives of this thesis include: 1) assess the individual and combined effects of a prebiotic and probiotic on metabolic health in obese rats; 2) determine the gut microbiota- dependent and -independent actions of the prebiotic oligofructose using a model of selective decontamination with antibiotics in obese rats; 3) examine the effectiveness of the prebiotic oligofructose for treatment of liver-biopsy confirmed non-alcoholic steatohepatitis (NASH) in a pilot clinical trial. Methods: Animal studies were conducted using diet-induced obese rats. Individuals with NASH were recruited by physicians from the Foothills Medical Centre. Body composition was measured with dual x-ray absorptiometry (DXA). Oral glucose tolerance tests (OGTTs) were conducted to measure glycemia. Markers of satiety, inflammation, and intestinal permeability were measured in blood. Gut microbiota was assessed using qPCR and 16S rRNA gene sequencing. Gene expression was measured using real time RT-PCR. Pre-post study liver biopsies were collected to assess histological changes in NASH. Results: The primary findings from our three study objectives were: 1) oligofructose, in comparison to Bifidobacterium animalis ssp. lactis BB-12, provides a more potent stimulus in reducing adiposity and modifying gut microbiota; 2) the ability of oligofructose to reduce adiposity and intestinal permeability is attenuated when Lactobacillus and Bifidobacterium growth is impeded with ampicillin in an animal model; 3) oligofructose supplementation improves histological measures of steatosis and has a tendency to decrease hepatocellular inflammation in individuals with NASH. Conclusion: Our results provide evidence for the role of prebiotics in correcting metabolic dysfunction in obesity. The findings from our pilot study provide the rationale for a larger-scale clinical trial assessing the effects of inulin type fructans and other prebiotics in NASH.en_US
dc.identifier.citationBomhof, M. (2016). Dietary Manipulation of Gut Microbiota for Improvement of Metabolic Health (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/25704en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/25704
dc.identifier.urihttp://hdl.handle.net/11023/3095
dc.language.isoeng
dc.publisher.facultyGraduate Studies
dc.publisher.facultyKinesiology
dc.publisher.institutionUniversity of Calgaryen
dc.publisher.placeCalgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subjectNutrition
dc.subject.classificationObesityen_US
dc.subject.classificationGut Microbiotaen_US
dc.subject.classificationPrebioticen_US
dc.subject.classificationProbioticen_US
dc.titleDietary Manipulation of Gut Microbiota for Improvement of Metabolic Health
dc.typedoctoral thesis
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameDoctor of Philosophy (PhD)
ucalgary.item.requestcopytrue
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