12 results on '"Emily R Davenport"'
Search Results
2. Genome-Wide Association Studies of the Human Gut Microbiota.
- Author
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Emily R Davenport, Darren A Cusanovich, Katelyn Michelini, Luis B Barreiro, Carole Ober, and Yoav Gilad
- Subjects
Medicine ,Science - Abstract
The bacterial composition of the human fecal microbiome is influenced by many lifestyle factors, notably diet. It is less clear, however, what role host genetics plays in dictating the composition of bacteria living in the gut. In this study, we examined the association of ~200K host genotypes with the relative abundance of fecal bacterial taxa in a founder population, the Hutterites, during two seasons (n = 91 summer, n = 93 winter, n = 57 individuals collected in both). These individuals live and eat communally, minimizing variation due to environmental exposures, including diet, which could potentially mask small genetic effects. Using a GWAS approach that takes into account the relatedness between subjects, we identified at least 8 bacterial taxa whose abundances were associated with single nucleotide polymorphisms in the host genome in each season (at genome-wide FDR of 20%). For example, we identified an association between a taxon known to affect obesity (genus Akkermansia) and a variant near PLD1, a gene previously associated with body mass index. Moreover, we replicate a previously reported association from a quantitative trait locus (QTL) mapping study of fecal microbiome abundance in mice (genus Lactococcus, rs3747113, P = 3.13 x 10-7). Finally, based on the significance distribution of the associated microbiome QTLs in our study with respect to chromatin accessibility profiles, we identified tissues in which host genetic variation may be acting to influence bacterial abundance in the gut.
- Published
- 2015
- Full Text
- View/download PDF
3. Seasonal variation in human gut microbiome composition.
- Author
-
Emily R Davenport, Orna Mizrahi-Man, Katelyn Michelini, Luis B Barreiro, Carole Ober, and Yoav Gilad
- Subjects
Medicine ,Science - Abstract
The composition of the human gut microbiome is influenced by many environmental factors. Diet is thought to be one of the most important determinants, though we have limited understanding of the extent to which dietary fluctuations alter variation in the gut microbiome between individuals. In this study, we examined variation in gut microbiome composition between winter and summer over the course of one year in 60 members of a founder population, the Hutterites. Because of their communal lifestyle, Hutterite diets are similar across individuals and remarkably stable throughout the year, with the exception that fresh produce is primarily served during the summer and autumn months. Our data indicate that despite overall gut microbiome stability within individuals over time, there are consistent and significant population-wide shifts in microbiome composition across seasons. We found seasonal differences in both (i) the abundance of particular taxa (false discovery rate
- Published
- 2014
- Full Text
- View/download PDF
4. Taxonomic classification of bacterial 16S rRNA genes using short sequencing reads: evaluation of effective study designs.
- Author
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Orna Mizrahi-Man, Emily R Davenport, and Yoav Gilad
- Subjects
Medicine ,Science - Abstract
Massively parallel high throughput sequencing technologies allow us to interrogate the microbial composition of biological samples at unprecedented resolution. The typical approach is to perform high-throughout sequencing of 16S rRNA genes, which are then taxonomically classified based on similarity to known sequences in existing databases. Current technologies cause a predicament though, because although they enable deep coverage of samples, they are limited in the length of sequence they can produce. As a result, high-throughout studies of microbial communities often do not sequence the entire 16S rRNA gene. The challenge is to obtain reliable representation of bacterial communities through taxonomic classification of short 16S rRNA gene sequences. In this study we explored properties of different study designs and developed specific recommendations for effective use of short-read sequencing technologies for the purpose of interrogating bacterial communities, with a focus on classification using naïve Bayesian classifiers. To assess precision and coverage of each design, we used a collection of ∼8,500 manually curated 16S rRNA gene sequences from cultured bacteria and a set of over one million bacterial 16S rRNA gene sequences retrieved from environmental samples, respectively. We also tested different configurations of taxonomic classification approaches using short read sequencing data, and provide recommendations for optimal choice of the relevant parameters. We conclude that with a judicious selection of the sequenced region and the corresponding choice of a suitable training set for taxonomic classification, it is possible to explore bacterial communities at great depth using current technologies, with only a minimal loss of taxonomic resolution.
- Published
- 2013
- Full Text
- View/download PDF
5. The microbiome of diverticulitis
- Author
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Nimalan Jeganathan, Gregory S. Yochum, Emily R. Davenport, and Walter A. Koltun
- Subjects
medicine.medical_specialty ,Physiology ,business.industry ,Confounding ,Fecal bacteriotherapy ,Diverticulitis ,medicine.disease ,Rifaximin ,Uncomplicated diverticulitis ,chemistry.chemical_compound ,chemistry ,Physiology (medical) ,medicine ,Limited evidence ,Microbiome ,business ,Intensive care medicine ,Dysbiosis - Abstract
Despite a marked impact on society in terms of patient suffering and healthcare expenditure, colonic diverticulitis has a relative scarcity of published literature examining its pathophysiology. Based on preliminary studies, akin to other gastrointestinal diseases, alterations of the microbiome appear to be associated with diverticulitis. In fact, these perturbations in the microbiome can be detected when comparing segments of diseased and non-diseased colonic tissues within the same individual. Unfortunately, differentiating cause from effect is not feasible without longitudinal studies. While the use of antibiotics for the treatment of uncomplicated diverticulitis is waning, studies utilizing rifaximin, probiotics, and even fecal microbiota transplantation are growing. At present, treatment recommendations are limited by significant heterogeneity in the study populations as well as confounding bias. Ultimately, while dysbiosis is likely to play a role in diverticulitis, a lack of animal models upon which to perform mechanistic study has limited evidence-based recommendations.
- Published
- 2021
6. Integrated analysis of population genomics, transcriptomics and virulence provides novel insights into Streptococcus pyogenes pathogenesis
- Author
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Andrew G. Clark, Jaana Vuopio, Marita Debess Magnussen, Johan Pensar, Hoang A. T. Nguyen, Kirsi Gröndahl-Yli-Hannuksela, Randall J. Olsen, Stephen B. Beres, Emily R. Davenport, Hackwon Do, Shahin Gaini, Maiju Pesonen, Magnus Gottfredsson, Samantha L. Kubiak, Luchang Zhu, Matthew Ojeda Saavedra, James M. Musser, Dominique A. Caugant, Benjamin Strope, Frank R. DeLeo, Jukka Corander, Paul E. Bernard, Jesus M. Eraso, Adeline R. Porter, Karl G. Kristinsson, Concepcion C. Cantu, S. Wesley Long, Waleed Nasser, Priyanka Kachroo, Maria Jose Arredondo, and Muthiah Kumaraswami
- Subjects
Streptococcus pyogenes ,Quantitative Trait Loci ,Virulence ,Biology ,medicine.disease_cause ,Genome ,Article ,Transcriptome ,Population genomics ,03 medical and health sciences ,0302 clinical medicine ,Intergenic region ,Genetics ,medicine ,Indel ,Phylogeny ,030304 developmental biology ,0303 health sciences ,Gene Expression Regulation, Bacterial ,Genomics ,3. Good health ,Expression quantitative trait loci ,030217 neurology & neurosurgery ,Genome, Bacterial ,Genome-Wide Association Study - Abstract
Streptococcus pyogenes causes 700 million human infections annually worldwide, yet, despite a century of intensive effort, there is no licensed vaccine against this bacterium. Although a number of large-scale genomic studies of bacterial pathogens have been published, the relationships among the genome, transcriptome, and virulence in large bacterial populations remain poorly understood. We sequenced the genomes of 2,101 emm28 S. pyogenes invasive strains, from which we selected 492 phylogenetically diverse strains for transcriptome analysis and 50 strains for virulence assessment. Data integration provided a novel understanding of the virulence mechanisms of this model organism. Genome-wide association study, expression quantitative trait loci analysis, machine learning, and isogenic mutant strains identified and confirmed a one-nucleotide indel in an intergenic region that significantly alters global transcript profiles and ultimately virulence. The integrative strategy that we used is generally applicable to any microbe and may lead to new therapeutics for many human pathogens. This study presents the genomes of 2,101 emm28 Streptococcus pyogenes invasive strains, of which 492 were transcriptionally profiled, and 50 were assessed for virulence. GWAS, eQTL analysis, and study of isogenic mutant strains identified an intergenic region that alters global transcript profiles and bacterial virulence.
- Published
- 2019
7. Genetic determinants of the gut microbiome in UK twins
- Author
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Rob Knight, Jordana T. Bell, Michelle Beaumont, Andrew G. Clark, Matthew A. Jackson, Emily R. Davenport, Julia K. Goodrich, Carole Ober, Tim D. Spector, and Ruth E. Ley
- Subjects
Male ,0301 basic medicine ,Candidate gene ,medicine.medical_treatment ,Immunology ,Microbial Consortia ,Twins ,Biology ,Microbiology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Clinical Research ,Virology ,Genetic variation ,Genetics ,medicine ,2.1 Biological and endogenous factors ,Humans ,Microbiome ,Aetiology ,Gene ,Nutrition ,Base Sequence ,Human Genome ,Gastrointestinal Microbiome ,Genetic Variation ,Lactase ,Heritability ,Twin study ,United Kingdom ,030104 developmental biology ,Medical Microbiology ,Female ,Parasitology ,030217 neurology & neurosurgery ,Biotechnology - Abstract
Summary Studies in mice and humans have revealed intriguing associations between host genetics and the microbiome. Here we report a 16S rRNA-based analysis of the gut microbiome in 1,126 twin pairs, a subset of which was previously reported. Tripling the sample narrowed the confidence intervals around heritability estimates and uncovered additional heritable taxa, some of which are validated in other studies. Repeat sampling of subjects showed heritable taxa to be temporally stable. A candidate gene approach uncovered associations between heritable taxa and genes related to diet, metabolism, and olfaction. We replicate an association between Bifidobacterium and the lactase (LCT) gene locus and identify an association between the host gene ALDH1L1 and the bacteria SHA-98, suggesting a link between formate production and blood pressure. Additional genes detected are involved in barrier defense and self/non-self recognition. Our results indicate that diet-sensing, metabolism, and immune defense are important drivers of human-microbiome co-evolution.
- Published
- 2018
8. Heritable components of the human fecal microbiome are associated with visceral fat
- Author
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Michelle Beaumont, Massimo Mangino, Matthew A. Jackson, Tess Pallister, Julia K. Goodrich, Jordana T. Bell, Sara Vieira-Silva, Rob Knight, Idil Yet, Andrew G. Clark, Ruth E. Ley, Jeroen Raes, Justine W. Debelius, Emily R. Davenport, and Tim D. Spector
- Subjects
0301 basic medicine ,Aging ,Bioinformatics ,Population ,Twins ,Gut flora ,Cardiovascular ,Oral and gastrointestinal ,Heritability ,03 medical and health sciences ,fluids and secretions ,0302 clinical medicine ,Clinical Research ,Information and Computing Sciences ,Genetics ,medicine ,2.1 Biological and endogenous factors ,Obesity ,Visceral fat ,Microbiome ,Aetiology ,education ,Metabolic and endocrine ,Nutrition ,Cancer ,Genetic association ,2. Zero hunger ,education.field_of_study ,biology ,Prevention ,Research ,Human Genome ,Biological Sciences ,medicine.disease ,biology.organism_classification ,3. Good health ,Stroke ,030104 developmental biology ,Cohort ,Fecal microbiome ,Body mass index ,Environmental Sciences ,030217 neurology & neurosurgery - Abstract
Background Variation in the human fecal microbiota has previously been associated with body mass index (BMI). Although obesity is a global health burden, the accumulation of abdominal visceral fat is the specific cardio-metabolic disease risk factor. Here, we explore links between the fecal microbiota and abdominal adiposity using body composition as measured by dual-energy X-ray absorptiometry in a large sample of twins from the TwinsUK cohort, comparing fecal 16S rRNA diversity profiles with six adiposity measures. Results We profile six adiposity measures in 3666 twins and estimate their heritability, finding novel evidence for strong genetic effects underlying visceral fat and android/gynoid ratio. We confirm the association of lower diversity of the fecal microbiome with obesity and adiposity measures, and then compare the association between fecal microbial composition and the adiposity phenotypes in a discovery subsample of twins. We identify associations between the relative abundances of fecal microbial operational taxonomic units (OTUs) and abdominal adiposity measures. Most of these results involve visceral fat associations, with the strongest associations between visceral fat and Oscillospira members. Using BMI as a surrogate phenotype, we pursue replication in independent samples from three population-based cohorts including American Gut, Flemish Gut Flora Project and the extended TwinsUK cohort. Meta-analyses across the replication samples indicate that 8 OTUs replicate at a stringent threshold across all cohorts, while 49 OTUs achieve nominal significance in at least one replication sample. Heritability analysis of the adiposity-associated microbial OTUs prompted us to assess host genetic-microbe interactions at obesity-associated human candidate loci. We observe significant associations of adiposity-OTU abundances with host genetic variants in the FHIT, TDRG1 and ELAVL4 genes, suggesting a potential role for host genes to mediate the link between the fecal microbiome and obesity. Conclusions Our results provide novel insights into the role of the fecal microbiota in cardio-metabolic disease with clear potential for prevention and novel therapies. Electronic supplementary material The online version of this article (doi:10.1186/s13059-016-1052-7) contains supplementary material, which is available to authorized users.
- Published
- 2016
9. Nasal Microbiome Composition Is Associated with Chitotriosidase (Chit1) Activity in Adult Hutterites
- Author
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Geoff L. Chupp, Catherine Igartua, Jack A. Elias, Emily R. Davenport, Jayant M. Pinto, Carole Ober, and Yoav Gilad
- Subjects
0301 basic medicine ,Pulmonary and Respiratory Medicine ,03 medical and health sciences ,Abstracts ,030104 developmental biology ,business.industry ,MEDLINE ,Medicine ,Microbiome ,business ,Bioinformatics ,Composition (language) - Published
- 2016
10. Seasonal variation in human gut microbiome composition
- Author
-
Emily R. Davenport, Carole Ober, Katelyn Michelini, Luis B. Barreiro, Orna Mizrahi-Man, and Yoav Gilad
- Subjects
Male ,Anatomy and Physiology ,Clinical Pathology ,Firmicutes ,Biodiversity ,lcsh:Medicine ,Gastroenterology and Hepatology ,Microbiology ,Microbial Ecology ,Diversity index ,Feces ,Abundance (ecology) ,Diagnostic Medicine ,Pathology ,Humans ,Microbiome ,lcsh:Science ,Biology ,2. Zero hunger ,Multidisciplinary ,biology ,Ecology ,Population Biology ,Microbiota ,lcsh:R ,Age Factors ,Bacteroidetes ,Genomics ,biology.organism_classification ,Biota ,Gastrointestinal Tract ,Species Interactions ,Clinical Microbiology ,Community Ecology ,Metagenomics ,Metagenome ,Medicine ,lcsh:Q ,Female ,Seasons ,Digestive System ,Research Article - Abstract
The composition of the human gut microbiome is influenced by many environmental factors. Diet is thought to be one of the most important determinants, though we have limited understanding of the extent to which dietary fluctuations alter variation in the gut microbiome between individuals. In this study, we examined variation in gut microbiome composition between winter and summer over the course of one year in 60 members of a founder population, the Hutterites. Because of their communal lifestyle, Hutterite diets are similar across individuals and remarkably stable throughout the year, with the exception that fresh produce is primarily served during the summer and autumn months. Our data indicate that despite overall gut microbiome stability within individuals over time, there are consistent and significant population-wide shifts in microbiome composition across seasons. We found seasonal differences in both (i) the abundance of particular taxa (false discovery rate
- Published
- 2013
11. Genome-Wide Association Studies of the Human Gut Microbiota
- Author
-
Luis B. Barreiro, Yoav Gilad, Carole Ober, Darren A. Cusanovich, Katelyn Michelini, and Emily R. Davenport
- Subjects
Male ,medicine.medical_specialty ,Quantitative Trait Loci ,lcsh:Medicine ,Genome-wide association study ,Single-nucleotide polymorphism ,Biology ,Quantitative trait locus ,Polymorphism, Single Nucleotide ,Body Mass Index ,Feces ,Mice ,03 medical and health sciences ,0302 clinical medicine ,RNA, Ribosomal, 16S ,Molecular genetics ,Genetic variation ,Phospholipase D ,medicine ,Animals ,Humans ,Obesity ,Microbiome ,lcsh:Science ,030304 developmental biology ,2. Zero hunger ,Genetics ,0303 health sciences ,Multidisciplinary ,Bacteria ,Host (biology) ,lcsh:R ,Gastrointestinal Microbiome ,Biodiversity ,Gastrointestinal Tract ,Female ,lcsh:Q ,030217 neurology & neurosurgery ,Genome-Wide Association Study ,Research Article - Abstract
The bacterial composition of the human fecal microbiome is influenced by many lifestyle factors, notably diet. It is less clear, however, what role host genetics plays in dictating the composition of bacteria living in the gut. In this study, we examined the association of ~200K host genotypes with the relative abundance of fecal bacterial taxa in a founder population, the Hutterites, during two seasons (n = 91 summer, n = 93 winter, n = 57 individuals collected in both). These individuals live and eat communally, minimizing variation due to environmental exposures, including diet, which could potentially mask small genetic effects. Using a GWAS approach that takes into account the relatedness between subjects, we identified at least 8 bacterial taxa whose abundances were associated with single nucleotide polymorphisms in the host genome in each season (at genome-wide FDR of 20%). For example, we identified an association between a taxon known to affect obesity (genus Akkermansia) and a variant near PLD1, a gene previously associated with body mass index. Moreover, we replicate a previously reported association from a quantitative trait locus (QTL) mapping study of fecal microbiome abundance in mice (genus Lactococcus, rs3747113, P = 3.13 x 10−7). Finally, based on the significance distribution of the associated microbiome QTLs in our study with respect to chromatin accessibility profiles, we identified tissues in which host genetic variation may be acting to influence bacterial abundance in the gut.
- Published
- 2015
12. Decrease in Diversity of Nasal Microbiota during Wheezing Episodes in Preschool Children
- Author
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Carole Ober, Katherine A. Naughton, Gorka Alkorta-Aranburu, David M. Mauger, So Watanabe, Daniel J. Jackson, Jayant M. Pinto, Emily R. Davenport, Yoav Gilad, Robert F. Lemanske, and Catherine Igartua
- Subjects
Pediatrics ,medicine.medical_specialty ,Future studies ,biology ,Respiratory tract infections ,business.industry ,Public health ,education ,Immunology ,Fusobacteria ,Inhaled corticosteroids ,biology.organism_classification ,medicine.disease ,medicine.anatomical_structure ,medicine ,Immunology and Allergy ,Microbiome ,business ,Nose ,Asthma - Abstract
T U E S D A Y 890 Decrease in Diversity of Nasal Microbiota during Wheezing Episodes in Preschool Children Gorka Alkorta-Aranburu, PhD, Catherine Igartua, Emily R. Davenport, Katherine Naughton, So Watanabe, MD, PhD, Yoav Gilad, PhD, Robert F. Lemanske, Jr, MD, FAAAAI, David M. Mauger, PhD, Carole Ober, PhD, Daniel J. Jackson, MD, Jayant M. Pinto, MD; The University of Chicago, Showa University, Toyko, Japan, University of Chicago, University of Wisconsin School of Medicine and Public Health, Madison, WI, Penn State University College of Medicine, Hershey, PA, University of Chicago, Chicago, IL, Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, The University of Chicago, Chicago, IL. RATIONALE: Wheezing episodes are responsible for significant morbidity in children and are closely associated with respiratory tract infections (RTIs).We hypothesized that the composition of airway bacteria would be altered during these illnesses. METHODS: Using DNA from nasal lavage samples prospectively collected in the Maintenance and Intermittent Inhaled Corticosteroids in Wheezing Toddlers (MIST) clinical trial, we sequenced the 16S rRNA gene (V4 region) to analyze the bacterial microbiome of 33 children at baseline and during RTI. 160,000 sequence reads per sample were subsampled at random and classified using Mothur (RDP database) in order to generate standard ecologic metrics and identify the abundance of specific bacteria. RESULTS: Among the 18 males and 15 females (mean age 36 months), a majority had allergic sensitization (51.5%) or a parent with asthma (57.6%). Microbial diversity was significantly decreased during RTIs (Shannon Index 1.17 vs. 0.71, P50.018), particularly episodes severe enough to be treated with oral corticosteroids. The relative abundance of the phyla Bacteroidetes and Fusobacteria were lower during RTIs (Bonferroni P 0.01). CONCLUSIONS: Severe RTIs are associated with decreased bacterial diversity in the upper airway, indicating that the composition of nasal microbiota may influence wheezing episodes. Future studies should define the role of specific bacterial populations in these episodes. The nose is an accessible site to assess these relationships.
- Published
- 2015
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