Matching Items (3)
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- All Subjects: Microbiome
- Creators: Whisner, Corrie
Description
Obesity increases the risk for colorectal cancer. In mice, a pro-obesity high-fat-diet (HFD) leads to an intestinal phenotype characterized by enhanced proliferation, numbers, function and tumor-initiating capacity of stem cells, the cell-of-origin for many intestinal cancers. This phenotype is driven by a lipid metabolism program facilitated by an intrinsic Peroxisome Proliferator-Activated Receptor/Fatty Acid Oxidation (PPAR/FAO) axis that senses and utilizes cellular lipids. However, the microbiome is a known regulator of lipid metabolism in the gut, but little is understood about how the gut commensals affect access to the lipids and alter stem cell function. Here, we use the long term HFD-fed mouse model to analyze the phenotypic changes in the intestinal stem cells (ISCs) after depletion of the gut microbiota. We find that the loss of the gut microbiome after four weeks of antibiotic treatment imposes significant changes in ISC function leading to reduced HFD ISC regenerative potential. These results indicate that the gut microbiome plays a crucial role in the lipid metabolic process which regulates and maintains the HFD ISC phenotype, and further suggests that the gut microbiome may augment the diet-induced tumor initiating capacity by altering the stem cell function.
ContributorsSantos Molina, Pablo (Author) / Mana, Miyeko (Thesis director) / Whisner, Corrie (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / Historical, Philosophical & Religious Studies, Sch (Contributor)
Created2022-05
Description
The prevalence of obesity and obesity-related disorders have increased world-wide. In the last decade, the intestinal microbiome has become a major indicator of metabolic and gastrointestinal health. Previous research has shown that high-fat diet (HFD) consumption can alter the microbial composition of the gut by increasing the abundance of gram-positive bacteria associated with the onset of obesity and type 2 diabetes. Although, the most common form of obesity and metabolic syndrome intervention is exercise and diet, these recommendations may not improve severe cases of obesity. Thus, an important relevance of my project was to investigate whether the intake of an organometallic complex (OMC) would prevent the onset of metabolic and gastrointestinal complications associated with high-fat diet intake. I hypothesized that the consumption of a HFD for 6 weeks would promote the development of metabolic and gastrointestinal disease risk factors. Next, it was hypothesized that OMC treatment would decrease metabolic risk factors by improving insulin sensitivity and decreasing weight gain. Finally, I hypothesized that HFD-intake would increase the abundance of gram-positive bacteria associated with gastrointestinal disease. My preliminary data investigated the effects of a 6-week HFD on the development of hepatic steatosis, intestinal permeability and inflammation in male Sprague Dawley rats. I found that a 6-week HFD increases hepatic triglyceride concentrations, plasma endotoxins and promotes the production of pro-inflammatory cytokines in the cecum wall. I then investigated whether OMC treatment could prevent metabolic risk factors in male Sprague-Dawley rats fed a HFD for 10 weeks and found that OMC can mitigate risk factors such hyperglycemia, liver disease, impaired endothelial function, and inflammation. Lastly, I investigated the effects of a 10-week HFD on the gastrointestinal system and found an increase in liver triglycerides and free glycerol and alterations of the distal gut microbiome. My results support the hypothesis that a HFD can promote metabolic risk factors, alter the gut microbiome and increase systemic inflammation and that OMC treatment may help mitigate some of these effects. Together, these studies are among the first to demonstrate the effects of a soil-derived compound on metabolic complications. Additionally, these conclusions also provide an essential basis for future gastrointestinal and microbiome studies of OMC treatment.
ContributorsCrawford, Meli'sa Shaunte (Author) / Sweazea, Karen L (Thesis advisor) / Deviche, Pierre (Thesis advisor) / Al-Nakkash, Layla (Committee member) / Whisner, Corrie (Committee member) / Hyatt, Jon-Philippe (Committee member) / Arizona State University (Publisher)
Created2019
Description
College weight gain and obesity are significant problems impacting our society, leading to a considerable number of comorbidities during and after college. Gut microbiota are increasingly recognized for their role in obesity and weight gain. Currently, research exploring the gut microbiome and its associations with dietary intake and body mass index (BMI) is limited among this population. Therefore, the purpose of this study was to assess associations between the gut microbiome, BMI, and dietary intake in a population of healthy college students living in two dorms at Arizona State University (n=90). Cross-sectional analyses were undertaken including 24-hour dietary recalls and anthropometrics (height, weight and BMI). High throughput Bacterial 16S rRNA gene sequencing of fecal samples was performed to quantify the gut microbiome and analyses were performed at phyla and family levels. Within this population, the mean BMI was 24.4 ± 5.3 kg/m2 and mean caloric intake was 1684 ± 947 kcals/day. Bacterial community analysis revealed that there were four predominant phyla and 12 predominant families accounting for 99.3% and 97.1% of overall microbial communities, respectively. Results of this study suggested that a significant association occurred between one principal component (impacted most by 22 microbial genera primarily within Firmicutes) and BMI (R2=0.053, p=0.0301). No significant correlations or group differences were observed when assessing the Firmicutes/Bacteroidetes ratio in relation to BMI or habitual dietary intake. These results provide a basis for gut microbiome research in college populations. Although, findings suggest that groups of microbial genera may be most influential in obesity, further longitudinal research is necessary to more accurately describe these associations over me. Findings from future research may be used to develop interventions to shift the gut microbiome to help moderate or prevent excess weight gain during this important life stage.
ContributorsHotz, Ricci-Lee (Author) / Whisner, Corrie (Thesis advisor) / Bruening, Meredith (Committee member) / Vega-Lopez, Sonia (Committee member) / Lespron, Christy (Committee member) / Arizona State University (Publisher)
Created2016