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Description
Obesity is a worldwide epidemic accompanied by multiple comorbidities. Bariatric surgery is currently the most efficient treatment for morbid obesity and its comorbidities. The etiology of obesity is unknown, although genetic, environmental, and most recently, microbiome elements have been recognized as contributors to this rising epidemic. The role of the gut microbiome in weight-loss or weight-gain warrants investigation, and bariatric surgery provides a good model to study influences of the microbiome on host metabolism. The underlying goals of my research were to analyze (i) the factors that change the microbiome after bariatric surgery, (ii) the effects of different types of bariatric surgeries on the gut microbiome and metabolism, (iii) the role of the microbiome on the success of bariatric surgery, and (iv) temporal and spatial changes of the microbiome after bariatric surgery.
Roux-en-Y gastric bypass (RYGB) rearranges the gastrointestinal tract and reduces gastric acid secretions. Therefore, pH could be one of the factors that change microbiome after RYGB. Using mixed-cultures and co-cultures of species enriched after RYGB, I showed that as small as 0.5 units higher gut pH can aid in the survival of acid-sensitive microorganisms after RYGB and alter gut microbiome function towards the production of weight loss-associated metabolites. By comparing microbiome after two different bariatric surgeries, RYGB and laparoscopic adjustable gastric banding (LAGB), I revealed that gut microbiome structure and metabolism after RYGB are remarkably different than LAGB, and LAGB change microbiome minimally. Given the distinct RYGB alterations to the microbiome, I examined the contribution of the microbiome to weight loss. Analyses revealed that Fusobacterium might lessen the success of RYGB by producing putrescine, which may enhance weight-gain and could serve as biomarker for unsuccessful RYGB.
Finally, I showed that RYGB alters the luminal and the mucosal microbiome. Changes in gut microbial metabolic products occur in the short-term and persist over the long-term. Overall, the work in this dissertation provides insight into how the gut microbiome structure and function is altered after bariatric surgery, and how these changes potentially affect the host metabolism. These findings will be helpful in subsequent development of microbiome-based therapeutics to treat obesity.
Roux-en-Y gastric bypass (RYGB) rearranges the gastrointestinal tract and reduces gastric acid secretions. Therefore, pH could be one of the factors that change microbiome after RYGB. Using mixed-cultures and co-cultures of species enriched after RYGB, I showed that as small as 0.5 units higher gut pH can aid in the survival of acid-sensitive microorganisms after RYGB and alter gut microbiome function towards the production of weight loss-associated metabolites. By comparing microbiome after two different bariatric surgeries, RYGB and laparoscopic adjustable gastric banding (LAGB), I revealed that gut microbiome structure and metabolism after RYGB are remarkably different than LAGB, and LAGB change microbiome minimally. Given the distinct RYGB alterations to the microbiome, I examined the contribution of the microbiome to weight loss. Analyses revealed that Fusobacterium might lessen the success of RYGB by producing putrescine, which may enhance weight-gain and could serve as biomarker for unsuccessful RYGB.
Finally, I showed that RYGB alters the luminal and the mucosal microbiome. Changes in gut microbial metabolic products occur in the short-term and persist over the long-term. Overall, the work in this dissertation provides insight into how the gut microbiome structure and function is altered after bariatric surgery, and how these changes potentially affect the host metabolism. These findings will be helpful in subsequent development of microbiome-based therapeutics to treat obesity.
ContributorsIlhan, Zehra Esra (Author) / Krajmalnik-Brown, Rosa (Thesis advisor) / DiBaise, John K. (Committee member) / Cadillo-Quiroz, Hinsby (Committee member) / Rittmann, Bruce E. (Committee member) / Arizona State University (Publisher)
Created2016
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