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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

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.
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
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Historically, researchers in the gut microbiome have deemed the composition of the microbiome as being adult by the age of two. However, recent studies have contradicted this, demonstrating statistically significant differences in the microbiome even through childhood and adolescence. This difference is important in the field of microbiome research, particularly

Historically, researchers in the gut microbiome have deemed the composition of the microbiome as being adult by the age of two. However, recent studies have contradicted this, demonstrating statistically significant differences in the microbiome even through childhood and adolescence. This difference is important in the field of microbiome research, particularly in studies examining this relationship with weight, because even though there have been significant associations between the gut microbiome and weight, they have been largely studied in adults. The freshman year of college is an interesting time to study this relationship in younger populations, due to the lifestyle changes that make them vulnerable to weight gain. This study included N=139 participants, a majority female (N=97, 69.8%), white (N=59, 42.4%), and non-Hispanic (N=89, 64%). Participants were only included in this analysis if they gave 2 or more fecal samples over the 4 timepoint study. Samples were sequenced using the Illumina MiSeq instrument after polymerase chain reaction (PCR) amplification was performed on the V4 region of the 16S rRNA gene sequence. Statistical analysis was performed using the longitudinal plugin of QIIME2. Results demonstrate that low abundance features seemed to drive a majority of the differences in variability between those who maintained their weight over the course of the study and those who gained weight. This was demonstrated through many significant Unweighted UniFrac results with corresponding nonsignificant Weighted UniFrac data. This study demonstrated that changes in lower abundance features may have driven the significant differences in weight status in this study. This study emphasized the importance of low abundance features and how this relates to changes in weight status during a period of major lifestyle changes. Further work is needed to confirm these findings and explore how gut microbes change in free-living individuals gaining weight over time.
ContributorsAhern, Mary (Author) / Whisner, Corrie (Thesis advisor) / Bruening, Meg (Committee member) / Sears, Dorothy (Committee member) / Arizona State University (Publisher)
Created2021
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Background:The second an individual is born, the gut microbiome starts acquiring unique characteristics, including microbial richness and evenness. In addition, it has been found that during infancy, the mode of delivery, antibiotic exposure, feeding patterns, and environment play a role in such development. However, infancy is still an understudied population

Background:The second an individual is born, the gut microbiome starts acquiring unique characteristics, including microbial richness and evenness. In addition, it has been found that during infancy, the mode of delivery, antibiotic exposure, feeding patterns, and environment play a role in such development. However, infancy is still an understudied population related to the gut microbiota, specifically its’ connection to two modifiable factors-sleep-wake patterns and its’ interconnection with feeding practices in the first year of life. Methods: This secondary data analysis from a randomized longitudinal intervention study assessed the efficacy of a home-based education program in preventing the onset of childhood obesity. A convenience sample of 40 Hispanic mother and infant dyads were recruited to participate in an additional collection of fecal samples to evaluate associations between lifestyle/behavioral factors in infancy and gut microbiome composition in toddlerhood. Total sleep duration and feeding practices (breastmilk and formula) were assessed at one, six, and twelve months. In addition, alpha and beta diversity metrics were assessed from infant stool samples collected at 36 months. Results: This study found some significant and trending values for pairwise comparisons of alpha (Shannon Diversity Index) and beta (Bray Curtis and Jaccard Distance). Sleep-wake adequacy consisted of 14-17 total hours of sleep in 24 hours at one month and 12-16 hours for six and twelve months of age. No significant values were identified at one month of age. However, six and twelve months demonstrated significant observations for gut microbial richness and evenness. Trending differences (p=.06, Shannon Diversity Index) persisted in infants receiving adequate sleep at six months but for different feeding modalities. Faith’s PD, Pielou’s measure, and observed OTUs were three additional alpha-diversity metrics performed in all groups. Observed OTUs (p=.03) and Faith’s PD (p=.03) were significant at twelve months, demonstrating an increased microbial feature in infants receiving adequate sleep. Conclusion: The findings from this study may show how different timestamps in the first year of life may create gut microbial milestones. However, the interrelation between sleep-wake patterns, feeding modalities, and gut microbiome development is limited; further investigation is needed to monitor close changes and potentially create a criterion
ContributorsAlanis, Victoria (Author) / Whisner, Corrie M. (Thesis advisor) / Petrov, Megan E. (Committee member) / Bruening, Meg (Committee member) / Arizona State University (Publisher)
Created2022