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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
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The transition to college has been identified as a vulnerable period for weight gain and the onset of obesity. Research has shown that the gut microbiota is different in obese compared to lean individuals, but a period of weight gain has never been studied in free-living individuals. The objective of

The transition to college has been identified as a vulnerable period for weight gain and the onset of obesity. Research has shown that the gut microbiota is different in obese compared to lean individuals, but a period of weight gain has never been studied in free-living individuals. The objective of this longitudinal, observational study was to assess the association between changes in the intestinal microbiota and weight-related outcomes in healthy college students living in on-campus dormitories at Arizona State University (n=39). Anthropometric measures and fecal samples were collected at the beginning and end of the school year, and microbial relative abundance for A. muciniphila, F. prausnitzii, R. gnavus, and L. acidophilus was measured through qPCR analyses. In this population, body mass index (BMI) and waist circumference (WC) increased by 0.97 ± 1.28 kg/m2 and 2.64 ± 4.90 cm, respectively. Wilcoxon-Rank tests revealed that R. gnavus fold change was significantly different between groups of weight loss/maintenance and weight gain ≥ 5% body weight (0.14 [-0.21, 0.64], n=24 vs. -0.14 [-0.92, 0.05], n=15, respectively; p=0.028). Correlation analyses suggested a significant negative association between A. muciniphila fold change and both % WC change and % BMI change (r= -0.66; p<0.01 and r= -0.33; p=0.04, respectively). However, multivariate regression analysis controlling for sex and race/ethnicity showed a significant association between A. muciniphila and % WC change, but not % BMI change (R2= 0.53; p<0.01 and R2= 0.24; p=0.15). F. prausnitzii was not associated with weight-related outcomes in this sample. L. acidophilus was excluded from study analyses after subsequent qPCR trials revealed no amplification in participant samples. Overall, this was the first study to show a relationship between A. muciniphila fold change and weight-related outcomes over a period of weight gain. Specifically, A. muciniphila was strongly negatively associated with WC in this sample. Further research is needed to more accurately describe these associations and potential mechanisms associated with the shift in gut microbiota observed with weight gain. Findings from future research may be used to develop interventions for college students aiming to shift the gut microbiota to prevent weight gain.
ContributorsJourney, Elizabeth (Author) / Whisner, Corrie M (Thesis advisor) / Bruening, Meredith (Committee member) / Sweazea, Karen (Committee member) / Arizona State University (Publisher)
Created2017
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The microbiome and the immune system are known to work in conjunction to modulate the clearance of pathogens and tolerance of beneficial microbes. A growing area of research seeks to study the potential extent of the involvement of the microbiome in modulating and supporting the immune system during acute allograft

The microbiome and the immune system are known to work in conjunction to modulate the clearance of pathogens and tolerance of beneficial microbes. A growing area of research seeks to study the potential extent of the involvement of the microbiome in modulating and supporting the immune system during acute allograft rejection. It has been hypothesized that the localized microbiota in each organ produce metabolites that instigate inflammatory immune responses, but whether microbiota interactions precipitate acute allograft rejection is unknown. Therefore, this study focuses on microbiome shifts in the gut and kidney after inducing acute renal transplant rejection in order to implicate gut dysbiosis as a precursor or supporter of allograft rejection. This study also subsequently explores the use of an immune-modulating protein in order to determine differences in the outcome of transplant rejection and potential differences in intestinal microbial load. This experiment sought to induce rejection in BALB/c mice through the use of C57BL/6 mouse renal slivers. Microbiome abundance was analyzed in all experimental groups. Understanding the role of the microbiome in transplant rejection has vast clinical implications and has the potential to enhance pre- and post-operative treatment, and immune management and quality of life following organ transplant.

ContributorsKokott, Kristiana Tara (Author) / Lim, Efrem (Thesis director) / Lucas, Alexandra (Committee member) / School of International Letters and Cultures (Contributor) / School of Life Sciences (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description

The microbiome and virome are known to interact within the human body which in turn modulates the health and disease of an individual. While these interactions have been largely studied in bodily sites such as the gastrointestinal tract, the microbiome and virome of the female genital tract (FGT) remains largely

The microbiome and virome are known to interact within the human body which in turn modulates the health and disease of an individual. While these interactions have been largely studied in bodily sites such as the gastrointestinal tract, the microbiome and virome of the female genital tract (FGT) remains largely understudied. Within the virome exists DNA and RNA viruses which are known to infect both eukaryotes and prokaryotes. While existing virome research within the FGT has focused largely on eukaryote infecting viruses, a large proportion of the virome consists of uncharacterized bacteriophages known as “dark matter”. Due to the lack of a specific gene marker for viruses, which is essential in qPCR quantification of other populations such as bacteria, determination of viral abundance and virome characterization has been limited. However, the staining of viral DNA has been found effective in visualizing and enumerating virus-like particles within various specimens. In this study, we seek to determine viral abundance within the FGT utilizing SYBR Gold nucleic acid stain to visualize VLP present within a cohort of cervicovaginal lavage (CVL) samples. Given these results we intend to draw conclusions regarding the interactions between the FGT virome and viral abundance as well as sexual-reproductive health. Understanding the complex relationship of the virome within the female reproductive tract is likely to have remarkable clinical implications and has the potential to progress both the diagnostic and treatment aspects of female sexual and reproductive health.

ContributorsFredenberg, Mara (Author) / Lim, Efrem (Thesis director) / Kaelin, Emily (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / School of International Letters and Cultures (Contributor)
Created2023-05