Background: 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.