Matching Items (9)

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Comparing Profiles of the Urinary Microbiome between Patients with Urinary Disease

Description

Urologic diseases interstitial cystitis (IC), overactive bladder (OAB), and urinary tract infection (UTI) affect tens of millions of people per year in the US alone. The human microbiome consists of

Urologic diseases interstitial cystitis (IC), overactive bladder (OAB), and urinary tract infection (UTI) affect tens of millions of people per year in the US alone. The human microbiome consists of a diverse community of bacteria (bacteriome) and viruses (virome) harbored in each individual that contributes to health and disease. Little is known about how the microbiome impacts urinary disorders. Using next-generation metagenomic sequencing, we characterized the urinary bacteriome and virome of patients with urinary disorders (IC, OAB, and UTI) and healthy controls. We show that the bacteriome was distinctly altered in patients by their respective urinary disorder. IC was characterized by a distinct prevalence of the genus Lactobacillus, while OAB was characterized by the genus Bacteroides, and UTI was characterized by Comamonas. IC, OAB, and UTI all also had significantly differed virome profiles from healthy individuals. In particular, we found that Lactobacillus phages were significantly associated with IC and Corynebacterium virus was associated with UTI samples, meanwhile no particular virus was correlated with OAB samples. Overall, we show that changes in the urinary microbiome are associated with incidence and spectrum of urinary diseases. These findings could lead to new microbiome modalities of treatment.

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Date Created
  • 2021-05

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Microbiome and Immune Modulation in Renal Subcapsular Allograft Acute Rejection

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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

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.

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Date Created
  • 2021-05

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Gut Bacterial Load Associates with Dramatic Declines in Anoxia Tolerance in Young Drosophila melanogaster Adults

Description

Anoxia tolerance is strongly correlated with tolerance to heat, desiccation, hyperosmotic shock, freezing, and other general stressors, suggesting that anoxia tolerance is broadly related to stress tolerance. Age affects the

Anoxia tolerance is strongly correlated with tolerance to heat, desiccation, hyperosmotic shock, freezing, and other general stressors, suggesting that anoxia tolerance is broadly related to stress tolerance. Age affects the capacity of many animals to survive anoxia, but the basis to this ontogenic variation is poorly understood. We exposed adult Drosophila, 1, 3, 5, 7, 9, and 12 days past eclosion, to six hours of anoxia and assessed survival 24-hours post-treatment. Survival of anoxia declined strongly with age (from 80% survival for one-day-old flies to 10% survival for 12 day-old-flies), a surprising result since adult fly senescence in Drosophila is usually observed much later. In anoxia, adenosine triphosphate (ATP) levels declined rapidly (< 30 min) to near-zero levels in both 1 and 12-day old adults; thus the higher anoxia-tolerance of young adults is not due to a better capacity to keep ATP elevated. Relatively few physiological parameters are reported to change over this age range in D. melanogaster, but gut bacterial content increases strongly. As a partial test for a causal link between bacterial load and anoxia tolerance, we replaced food daily, every third day, or every sixth day, and assayed survival of six hours of anoxia and bacterial load at 12 days of age. Anoxia tolerance for 12-day old flies was improved by more food changes and was strongly and negatively affected by bacterial load. These data suggest that increasing bacterial load may play an important role in the age-related decline of anoxia tolerance in Drosophila.

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Date Created
  • 2020

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Gut microbiome diversity and community structure following dietary genistein treatment in a murine model of cystic fibrosis

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

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.

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Date Created
  • 2019

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Microbial restoration ecology of biological soil crusts

Description

Biological soil crusts (biocrusts) are topsoil communities of organisms that contribute to soil fertility and erosion resistance in drylands. Anthropogenic disturbances can quickly damage these communities and their natural recovery

Biological soil crusts (biocrusts) are topsoil communities of organisms that contribute to soil fertility and erosion resistance in drylands. Anthropogenic disturbances can quickly damage these communities and their natural recovery can take decades. With the development of accelerated restoration strategies in mind, I studied physiological mechanisms controlling the establishment of cyanobacteria in biocrusts, since these photoautotrophs are not just the biocrust pioneer organisms, but also largely responsible for improving key soil attributes such as physical stability, nutrient content, water retention and albedo. I started by determining the cyanobacterial community composition of a variety of biocrust types from deserts in the Southwestern US. I then isolated a large number of cyanobacterial strains from these locations, pedigreed them based on their 16SrRNA gene sequences, and selective representatives that matched the most abundant cyanobacterial field populations. I then developed methodologies for large-scale growth of the selected isolates to produce location-specific and genetically autochthonous inoculum for restoration. I also developed and tested viable methodologies to physiologically harden this inoculum and improve its survival under harsh field conditions. My tests proved that in most cases good viability of the inoculum could be attained under field-like conditions. In parallel, I used molecular ecology approaches to show that the biocrust pioneer, Microcoleus vaginatus, shapes its surrounding heterotrophic microbiome, enriching for a compositionally-differentiated “cyanosphere” that concentrates the nitrogen-fixing function. I proposed that a mutualism based on carbon for nitrogen exchange between M. vaginatus and its cyanosphere creates a consortium that constitutes the true pioneer community enabling the colonization of nitrogen-poor, bare soils. Using the right mixture of photosynthetic and diazotrophic cultures will thus likely help in soil restoration. Additionally, using physiological assays and molecular meta-analyses, I demonstrated that the largest contributors to N2-fixation in late successional biocrusts (three genera of heterocystous cyanobacteria) partition their niche along temperature gradients, and that this can explain their geographic patterns of dominance within biocrusts worldwide. This finding can improve restoration strategies by incorporating climate-matched physiological types in inoculum formulations. In all, this dissertation resulted in the establishment of a comprehensive "cyanobacterial biocrust nursery", that includes a culture collection containing 101 strains, isolation and cultivation methods, inoculum design strategies as well as field conditioning protocols. It constitutes a new interdisciplinary application of microbiology in restoration ecology.

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Date Created
  • 2019

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Changes in Weight Status and the Intestinal Microbiota among College Students

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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

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.

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Date Created
  • 2017

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Are weight and diet related to the gut microbiome in healthy college students living in the dorms?: a cross-sectional observational analysis

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

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.

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Date Created
  • 2016

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Systematic Analysis of the Factors Contributing to the Variation and Change of the Microbiome

Description

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

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.

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Agent

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Date Created
  • 2018

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Examining the effects of a high fat diet on the development of metabolic syndrome and gut leakiness in male Sprague-Dawley rats

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

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.

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Agent

Created

Date Created
  • 2019