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Understanding changes and trends in biomedical knowledge is crucial for individuals, groups, and institutions as biomedicine improves people’s lives, supports national economies, and facilitates innovation. However, as knowledge changes what evidence illustrates knowledge changes? In the case of microbiome, a multi-dimensional concept from biomedicine, there are significant increases in publications,

Understanding changes and trends in biomedical knowledge is crucial for individuals, groups, and institutions as biomedicine improves people’s lives, supports national economies, and facilitates innovation. However, as knowledge changes what evidence illustrates knowledge changes? In the case of microbiome, a multi-dimensional concept from biomedicine, there are significant increases in publications, citations, funding, collaborations, and other explanatory variables or contextual factors. What is observed in the microbiome, or any historical evolution of a scientific field or scientific knowledge, is that these changes are related to changes in knowledge, but what is not understood is how to measure and track changes in knowledge. This investigation highlights how contextual factors from the language and social context of the microbiome are related to changes in the usage, meaning, and scientific knowledge on the microbiome. Two interconnected studies integrating qualitative and quantitative evidence examine the variation and change of the microbiome evidence are presented. First, the concepts microbiome, metagenome, and metabolome are compared to determine the boundaries of the microbiome concept in relation to other concepts where the conceptual boundaries have been cited as overlapping. A collection of publications for each concept or corpus is presented, with a focus on how to create, collect, curate, and analyze large data collections. This study concludes with suggestions on how to analyze biomedical concepts using a hybrid approach that combines results from the larger language context and individual words. Second, the results of a systematic review that describes the variation and change of microbiome research, funding, and knowledge are examined. A corpus of approximately 28,000 articles on the microbiome are characterized, and a spectrum of microbiome interpretations are suggested based on differences related to context. The collective results suggest the microbiome is a separate concept from the metagenome and metabolome, and the variation and change to the microbiome concept was influenced by contextual factors. These results provide insight into how concepts with extensive resources behave within biomedicine and suggest the microbiome is possibly representative of conceptual change or a preview of new dynamics within science that are expected in the future.
ContributorsAiello, Kenneth (Author) / Laubichler, Manfred D (Thesis advisor) / Simeone, Michael (Committee member) / Buetow, Kenneth (Committee member) / Walker, Sara I (Committee member) / Arizona State University (Publisher)
Created2018
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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

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
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Description
Introduction: Cystic fibrosis (CF) is the most common life-shortening autosomal recessive genetic disease affecting Caucasians. The disease is characterized by a dysfunctional cystic fibrosis transmembrane regulator (CFTR) protein and aberrant mucus accumulation that subsequently alters the physicochemical environment in numerous organ systems. These mucosal perturbations have been associated with inflammation

Introduction: Cystic fibrosis (CF) is the most common life-shortening autosomal recessive genetic disease affecting Caucasians. The disease is characterized by a dysfunctional cystic fibrosis transmembrane regulator (CFTR) protein and aberrant mucus accumulation that subsequently alters the physicochemical environment in numerous organ systems. These mucosal perturbations have been associated with inflammation and microbial dysbiosis, most notably in the lungs and gastrointestinal (GI) tract. Genistein, a soy isoflavone and dietary polyphenol, has been shown to modulate CFTR function in cell cultures and murine models, as well exert sex-dependent improvement of survival rates in a CF mouse model. However, it is unknown whether dietary genistein affects gut microbiome diversity and community structure in cystic fibrosis. This study sought to examine associations between dietary genistein treatment and gut microbiome diversity and community structure in a murine model of CF. Methods: Twenty-four male and female mice homozygous for the DF508 CFTR gene mutation were maintained on one of three diet regimens for a 45-day period (n=11, standard chow; n=7, Colyte-treated water and standard chow; n=6, 600 mg dietary genistein per kg body weight). One fecal pellet was collected per mouse post-treatment, and microbial genomic DNA was extracted from the fecal samples, quantified, amplified, and sequenced on the Illumina MiSeq platform. QIIME 2 was used to conduct alpha- and beta-diversity analyses on all samples. Results: Measures of alpha-diversity were significantly decreased in the dietary genistein group as compared to either standard chow or Colyte groups. Measures of beta-diversity showed that community structure differed significantly between dietary treatment groups; these differences were further illustrated by distinct clustering of taxa as shown by principal coordinates analysis plots. Conclusion: This 3-arm parallel experimental study showed that dietary genistein treatment was associated with decreased microbial diversity and differences in microbial community structure in DF508 mice.
ContributorsArgo, Katy Bryana (Author) / Whisner, Corrie M (Thesis advisor) / Al-Nakkash, Layla (Committee member) / Sweazea, Karen L (Committee member) / Arizona State University (Publisher)
Created2019