Jacques Ravel

University of Maryland, Baltimore, Baltimore, Maryland, United States

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Publications (188)1082.69 Total impact

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    Jacques Ravel, K Eric Wommack
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    ABSTRACT: We are deeply grateful to all of the names listed below, who reviewed manuscripts submitted to Microbiome in 2014. We hope that you all will continue to support the journal as a reviewer or, better yet, as a contributing author.
    12/2015; 3(1):4. DOI:10.1186/s40168-015-0068-7
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    Genome Research 05/2015; 25(5). DOI:10.1101/gr.187427.114 · 13.85 Impact Factor
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    ABSTRACT: Screening for colorectal cancer (CRC) and precancerous colorectal adenoma (CRA) can detect curable disease. However, participation in colonoscopy and sensitivity of fecal heme for CRA are low.
    04/2015; 142. DOI:10.1016/j.ebiom.2015.04.010
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    ABSTRACT: A mechanistic understanding of the purported health benefits conferred by consumption of probiotic bacteria has been limited by our knowledge of the resident gut microbiota and its interaction with the host. Here, we detail the impact of a single-organism probiotic, Lactobacillus rhamnosus GG ATCC 53103 (LGG), on the structure and functional dynamics (gene expression) of the gut microbiota in a study of 12 healthy individuals, 65 to 80 years old. The analysis revealed that while the overall community composition was stable as assessed by 16S rRNA profiling, the transcriptional response of the gut microbiota was modulated by probiotic treatment. Comparison of transcriptional profiles based on taxonomic composition yielded three distinct transcriptome groups that displayed considerable differences in functional dynamics. The transcriptional profile of LGG in vivo was remarkably concordant across study subjects despite the considerable interindividual nature of the gut microbiota. However, we identified genes involved in flagellar motility, chemotaxis, and adhesion from Bifidobacterium and the dominant butyrate producers Roseburia and Eubacterium whose expression was increased during probiotic consumption, suggesting that LGG may promote interactions between key constituents of the microbiota and the host epithelium. These results provide evidence for the discrete functional effects imparted by a specific single-organism probiotic and challenge the prevailing notion that probiotics substantially modify the resident microbiota within nondiseased individuals in an appreciable fashion. Probiotic bacteria have been used for over a century to promote digestive health. Many individuals report that probiotics alleviate a number of digestive issues, yet little evidence links how probiotic microbes influence human health. Here, we show how the resident microbes that inhabit the healthy human gut respond to a probiotic. The well-studied probiotic Lactobacillus rhamnosus GG ATCC 53103 (LGG) was administered in a clinical trial, and a suite of measurements of the resident microbes were taken to evaluate potential changes over the course of probiotic consumption. We found that LGG transiently enriches for functions to potentially promote anti-inflammatory pathways in the resident microbes. Copyright © 2015 Eloe-Fadrosh et al.
    mBio 04/2015; 6(2). DOI:10.1128/mBio.00231-15 · 6.88 Impact Factor
  • Gastroenterology 04/2015; 148(4):S-45. DOI:10.1016/S0016-5085(15)30156-6 · 13.93 Impact Factor
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    ABSTRACT: SINC, a new type III secreted protein of the avian and human pathogen, Chlamydia psittaci, uniquely targets the nuclear envelope of C. psittaci-infected cells and uninfected neighboring cells. Digitonin-permeabilization studies of infected or SINC-GFP-transfected HeLa cells indicate SINC targets the inner nuclear membrane. SINC localization at the nuclear envelope was blocked by importazole, confirming SINC import into the nucleus. Candidate partners were identified by proximity to biotin ligase-fused SINC in HeLa cells and mass spectrometry (BioID). This strategy identified 22 candidates with high confidence including the nucleoporin ELYS, lamin B1 and four proteins (emerin, MAN1, LAP1 and LBR) of the inner nuclear membrane, suggesting SINC interacts with host proteins that control nuclear structure, signaling, chromatin organization and gene silencing. GFP-SINC association with the native LEM-domain protein emerin, a conserved component of nuclear 'lamina' structure, or with a complex containing emerin, was confirmed by GFP pull-down. Our findings identify SINC as a novel bacterial protein that targets the nuclear envelope with the capability of globally altering nuclear envelope functions in the infected host cell and neighboring uninfected cells. These properties may contribute to the aggressive virulence of C. psittaci. © 2015 by The American Society for Cell Biology.
    Molecular biology of the cell 03/2015; 26(10). DOI:10.1091/mbc.E14-11-1530 · 5.98 Impact Factor
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    ABSTRACT: Although vaginal microbial communities of some healthy women have high proportions of Atopobium vaginae, the genus Atopobium is more commonly associated with bacterial vaginosis, a syndrome associated with an increased risk of adverse pregnancy outcomes and the transmission of sexually transmitted diseases. Genetic differences within Atopobium species may explain why single species can be associated with both health and disease. We used 16S rRNA gene sequences from previously published studies to explore the taxonomic diversity of the genus Atopobium in vaginal microbial communities of healthy women. Although A. vaginae was the species most commonly found, we also observed three other Atopobium species in the vaginal microbiota, one of which, A. parvulum, was not previously known to reside in the human vagina. Furthermore, we found several potential novel species of the genus Atopobium and multiple phylogenetic clades of Atopobium vaginae. The diversity of Atopobium found in our study, which focused only on samples from healthy women is greater than previously recognized, suggesting that analysis of samples from women with BV would yield even more diversity. Classification of microbes only to the genus level may thus obfuscate differences that might be important to better understand health or disease. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
    Foodborne Pathogens and Disease 03/2015; DOI:10.1093/femspd/ftv020 · 2.09 Impact Factor
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    ABSTRACT: In humans, the vaginal microbiota is thought to be the first line of defense again pathogens including Chlamydia trachomatis. The guinea pig has been extensively used as a model to study chlamydial infection because it shares anatomical and physiological similarities with humans, such as a squamous vaginal epithelium as well as some of the long-term outcomes caused by chlamydial infection. In this study, we aimed to evaluate the guinea pig - C. caviae model of genital infection as a surrogate for studying the role of the vaginal microbiota in the early steps of C. trachomatis infection in humans. We used culture-independent molecular methods to characterize the relative and absolute abundance of bacterial phylotypes in the guinea pig vaginal microbiota in animals non-infected, mock-infected or infected by C. caviae. We showed that the guinea pig and human vaginal microbiotas are of different bacterial composition and abundance. C. caviae infection had a profound effect on the absolute abundance of bacterial phylotypes but not on the composition of the guinea pig vaginal microbiota. Our findings compromise the validity of the guinea pig - C. caviae model to study the role of the vaginal microbiota during the early steps of sexually transmitted infection. © FEMS 2015. Published by Oxford University Press on behalf of FEMS. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com.
    Foodborne Pathogens and Disease 03/2015; 73(4). DOI:10.1093/femspd/ftv019 · 2.09 Impact Factor
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    ABSTRACT: Objective Despite widespread use of antibiotics for the treatment of life-threatening infections and for research on the role of commensal microbiota, our understanding of their effects on the host is still very limited. Design Using a popular mouse model of microbiota depletion by a cocktail of antibiotics, we analysed the effects of antibiotics by combining intestinal transcriptome together with metagenomic analysis of the gut microbiota. In order to identify specific microbes and microbial genes that influence the host phenotype in antibiotic-treated mice, we developed and applied analysis of the transkingdom network. Results We found that most antibiotic-induced alterations in the gut can be explained by three factors: depletion of the microbiota; direct effects of antibiotics on host tissues and the effects of remaining antibiotic-resistant microbes. Normal microbiota depletion mostly led to downregulation of different aspects of immunity. The two other factors (antibiotic direct effects on host tissues and antibiotic-resistant microbes) primarily inhibited mitochondrial gene expression and amounts of active mitochondria, increasing epithelial cell death. By reconstructing and analysing the transkingdom network, we discovered that these toxic effects were mediated by virulence/quorum sensing in antibiotic-resistant bacteria, a finding further validated using in vitro experiments. Conclusions In addition to revealing mechanisms of antibiotic-induced alterations, this study also describes a new bioinformatics approach that predicts microbial components that regulate host functions and establishes a comprehensive resource on what, why and how antibiotics affect the gut in a widely used mouse model of microbiota depletion by antibiotics.
    Gut 01/2015; DOI:10.1136/gutjnl-2014-308820 · 13.32 Impact Factor
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    ABSTRACT: For centuries, cholera has been one of the most feared diseases. The causative agent Vibrio cholerae is a waterborne Gram-negative enteric pathogen eliciting a severe watery diarrheal disease. In October 2010, the seventh pandemic reached Haiti, a country that had not experienced cholera for more than a century. By using whole-genome sequence typing and mapping strategies of 116 serotype O1 strains from global sources, including 44 Haitian genomes, we present a detailed reconstructed evolutionary history of the seventh pandemic with a focus on the Haitian outbreak. We catalogued subtle genomic alterations at the nucleotide level in the genome core and architectural rearrangements from whole-genome map comparisons. Isolates closely related to the Haitian isolates caused several recent outbreaks in southern Asia. This study provides evidence for a single-source introduction of cholera from Nepal into Haiti followed by rapid, extensive, and continued clonal expansion. The phylogeographic patterns in both southern Asia and Haiti argue for the rapid dissemination of V. cholerae across the landscape necessitating real-time surveillance efforts to complement the whole-genome epidemiological analysis. As eradication efforts move forward, phylogeographic knowledge will be important for identifying persistent sources and monitoring success at regional levels. The results of molecular and epidemiological analyses of this outbreak suggest that an indigenous Haitian source of V. cholerae is unlikely and that an indigenous source has not contributed to the genomic evolution of this clade.
    mBio 11/2014; 5(6). DOI:10.1128/mBio.01721-14. · 6.88 Impact Factor
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    ABSTRACT: The human microbiome has become a recognized factor in promoting and maintaining health. We outline opportunities in interdisciplinary research, analytical rigor, standardization, and policy development for this relatively new and rapidly developing field. Advances in these aspects of the research community may in turn advance our understanding of human microbiome biology.
    Cell 10/2014; 159(2):227–230. DOI:10.1016/j.cell.2014.09.022 · 33.12 Impact Factor
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    ABSTRACT: Abstract Intravaginal practices (IVP) are common among African women and are associated with HIV acquisition. A behavioral intervention to reduce IVP is a potential new HIV risk-reduction strategy. Fifty-eight HIV-1-uninfected Kenyan women reporting IVP and 42 women who denied IVP were followed for 3 months. Women using IVP attended a skill-building, theory-based group intervention occurring weekly for 3 weeks to encourage IVP cessation. Vaginal swabs at each visit were used to detect yeast, to detect bacterial vaginosis, and to characterize the vaginal microbiota. Intravaginal insertion of soapy water (59%) and lemon juice (45%) was most common among 58 IVP women. The group-counseling intervention led to a decrease in IVP from 95% (54/58) at baseline to 0% (0/39) at month 3 (p=0.001). After 3 months of cessation, there was a reduction in yeast on vaginal wet preparation (22% to 7%, p=0.011). Women in the IVP group were more likely to have a Lactobacillus iners-dominated vaginal microbiota at baseline compared to controls [odds ratio (OR), 6.4, p=0.006] without significant change in the microbiota after IVP cessation. The group counseling intervention was effective in reducing IVP for 3 months. Reducing IVP may be important in itself, as well as to support effective use of vaginal microbicides, to prevent HIV acquisition.
    AIDS Research and Human Retroviruses 09/2014; 30(11). DOI:10.1089/aid.2013.0251 · 2.46 Impact Factor
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    ABSTRACT: Context: The gut microbiota may influence the risk of breast cancer through effects on endogenous estrogens. Objective: The objective of the study was to investigate whether urinary estrogens and estrogen metabolites are associated with the diversity and composition of the fecal microbiome. Design and Setting: This was a cross-sectional study among women enrolled in Kaiser Permanente of Colorado. Participants: A total of 60 women drawn from a random sample of healthy postmenopausal women (aged 55-69 y), without current or recent use of antibiotics or hormone therapy and no history of cancer or gastrointestinal disease participated in the study. Outcome Measures and Methods: Creatinine-standardized urinary estrogens (estrone and estradiol) and 13 hydroxylated estrogen metabolites were measured in spot urines by liquid chromatography-tandem mass spectrometry. The fecal microbiome was assessed using pyrosequencing of 16S rRNA amplicons. General linear models were used to test for associations of diversity and composition of the fecal microbiome with parent estrogen (estrone + estradiol), total estrogens, and estrogen metabolites and the ratio of estrogen metabolites to parent estrogen, which has been predictive of postmenopausal breast cancer risk in previous studies. Results: The ratio of metabolites to parents was directly associated with whole-tree phylogenetic diversity (R = 0.35, P= .01). Relative abundances of the order Clostridiale (R = 0.32, P= .02) and the genus Bacteroides (R = -0.30, P= .03) were also correlated with the ratio of metabolites to parents. Associations were independent of age, body mass index, and study design factors. Conclusions: Our data suggest that women with a more diverse gut microbiome exhibit an elevated urinary ratio of hydroxylated estrogen metabolites to parent estrogen. Further research is warranted to confirm and relate these findings to clinical disease.
    Journal of Clinical Endocrinology &amp Metabolism 09/2014; DOI:10.1210/jc.2014-2222 · 6.31 Impact Factor
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    ABSTRACT: Smoking has been identified in observational studies as a risk factor for bacterial vaginosis (BV), a condition defined in part by decimation of Lactobacillus spp. The anti-estrogenic effect of smoking and trace amounts of benzo[a]pyrene diol epoxide (BPDE) may predispose women to BV. BPDE increases bacteriophage induction in Lactobacillus spp. and is found in the vaginal secretions of smokers. We compared the vaginal microbiota between smokers and non-smokers and followed microbiota changes in a smoking cessation pilot study.
    BMC Infectious Diseases 08/2014; 14(1):471. DOI:10.1186/1471-2334-14-471 · 2.56 Impact Factor
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    ABSTRACT: Sequence analyses and subtyping of Bacillus anthracis strains from Georgia reveal a single distinct lineage (Aust94) that is ecologically established. Phylogeographic analysis and comparisons to a global collection reveals a clade that is mostly restricted to Georgia. Within this clade, many groups are found around the country, however at least one subclade is only found in the eastern part. This pattern suggests that dispersal into and out of Georgia has been rare and despite historical dispersion within the country, for at least for one lineage, current spread is limited.
    PLoS ONE 07/2014; 9(7):e102651. DOI:10.1371/journal.pone.0102651 · 3.53 Impact Factor
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    ABSTRACT: Objective Lactobacillus dominates the lower genital tract microbiota of many women, producing a low vaginal pH, and is important for healthy pregnancy outcomes and protection against several sexually transmitted pathogens. Yet, factors that promote Lactobacillus remain poorly understood. We hypothesized that the amount of free glycogen in the lumen of the lower genital tract is an important determinant of Lactobacillus colonization and a low vaginal pH. Methods Free glycogen in lavage samples was quantified. Pyrosequencing of the 16S rRNA gene was used to identify microbiota from 21 African American women collected over 8–11 years. Results Free glycogen levels varied greatly between women and even in the same woman. Samples with the highest free glycogen had a corresponding median genital pH that was significantly lower (pH 4.4) than those with low glycogen (pH 5.8; p<0.001). The fraction of the microbiota consisting of Lactobacillus was highest in samples with high glycogen versus those with low glycogen (median = 0.97 vs. 0.05, p<0.001). In multivariable analysis, having 1 vs. 0 male sexual partner in the past 6 months was negatively associated, while BMI ≥30 was positively associated with glycogen. High concentrations of glycogen corresponded to higher levels of L. crispatus and L. jensenii, but not L. iners. Conclusion These findings show that free glycogen in genital fluid is associated with a genital microbiota dominated by Lactobacillus, suggesting glycogen is important for maintaining genital health. Treatments aimed at increasing genital free glycogen might impact Lactobacillus colonization.
    PLoS ONE 07/2014; 9(7):e102467. DOI:10.1371/journal.pone.0102467 · 3.53 Impact Factor
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    ABSTRACT: It is not currently possible to predict the probability of whether a woman with a chlamydial genital infection will develop pelvic inflammatory disease (PID). To determine if specific biomarkers may be associated with distinct chlamydial pathotypes, we utilized two Chlamydia muridarum variants (C. muridarum Var001 [CmVar001] and CmVar004) that differ in their abilities to elicit upper genital tract pathology in a mouse model. CmVar004 has a lower growth rate in vitro and induces pathology in only 20% of C57BL/6 mouse oviducts versus 83.3% of oviducts in CmVar001-infected mice. To determine if chemokine and cytokine production within 24 h of infection is associated with the outcome of pathology, levels of 15 chemokines and cytokines were measured. CmVar004 infection induced significantly lower levels of CXCL1, CXCL2, tumor necrosis factor alpha (TNF-α), and CCL2 in comparison to CmVar001 infection with similar rRNA (rs16) levels for Chlamydiae. A combination of microRNA (miRNA) sequencing and quantitative real-time PCR (qRT-PCR) analysis of 134 inflammation-related miRNAs was performed 24 h postinfection to determine if the chemokine/cytokine responses would also be reflected in miRNA expression profiles. Interestingly, 12 miRNAs (miR-135a-5p, miR298-5p, miR142-3p, miR223-3p, miR299a-3p, miR147-3p, miR105, miR325-3p, miR132-3p, miR142-5p, miR155-5p, and miR-410-3p) were overexpressed during CmVar004 infection compared to CmVar001 infection, inversely correlating with the respective chemokine/cytokine responses. To our knowledge, this is the first report demonstrating that early biomarkers elicited in the host can differentiate between two pathological variants of chlamydiae and be predictive of upper tract disease.
    mBio 07/2014; 5(3). DOI:10.1128/mBio.01241-14 · 6.88 Impact Factor
  • The Journal of Infectious Diseases 06/2014; DOI:10.1093/infdis/jiu330 · 5.78 Impact Factor
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    ABSTRACT: BackgroundThis study was undertaken to determine whether the vaginal microbiota of pregnant women who subsequently had a spontaneous preterm delivery is different from that of women who had a term delivery.ResultsThis was a nested case–control study of pregnant women who had a term delivery (controls) and those who had a spontaneous preterm delivery before 34 weeks of gestation (cases). Samples of vaginal fluid were collected longitudinally and stored at −70°C until assayed. A microbial survey using pyrosequencing of V1-V3 regions of 16S rRNA genes was performed. We tested the hypothesis of whether the relative abundance of individual microbial species (phylotypes) was different between women who had a term versus preterm delivery. A suite of bioinformatic and statistical tools, including linear mixed effects models and generalized estimating equations, was used. We show that: 1) the composition of the vaginal microbiota during normal pregnancy changed as a function of gestational age, with an increase in the relative abundance of four Lactobacillus spp., and decreased in anaerobe or strict-anaerobe microbial species as pregnancy progressed; 2) no bacterial taxa differed in relative abundance between women who had a spontaneous preterm delivery and those who delivered at term; and 3) no differences in the frequency of the vaginal community state types (CST I, III, IV-B) between women who delivered at term and those who delivered preterm were detected.ConclusionsThe bacterial taxa composition and abundance of vaginal microbial communities, characterized with 16S rRNA gene sequence-based techniques, were not different in pregnant women who subsequently delivered a preterm neonate versus those who delivered at term.
    05/2014; 2:18. DOI:10.1186/2049-2618-2-18

Publication Stats

9k Citations
1,082.69 Total Impact Points

Institutions

  • 1994–2015
    • University of Maryland, Baltimore
      • Institute for Genome Sciences
      Baltimore, Maryland, United States
  • 2012
    • Harvard Medical School
      • Department of Microbiology and Immunobiology
      Boston, Massachusetts, United States
  • 2011
    • Indiana University Bloomington
      • Department of Biology
      Bloomington, Indiana, United States
    • University of Pittsburgh
      • Department of Biological Sciences
      Pittsburgh, Pennsylvania, United States
    • U.S. Food and Drug Administration
      Washington, Washington, D.C., United States
  • 2010
    • U.S. Army Medical Research Institute of Infectious Diseases
      Фредерик, Maryland, United States
  • 2009
    • Queensland University of Technology
      • Institute of Health and Biomedical Innovation
      Brisbane, Queensland, Australia
  • 2007–2009
    • J. Craig Venter Institute
      Maryland, United States
    • Northern Arizona University
      • Department of Biological Sciences
      Flagstaff, AZ, United States
  • 2008
    • University of Delaware
      • Delaware Biotechnology Institute
      Newark, DE, United States
  • 2006–2008
    • Biomedical Research Institute, Rockville
      Роквилл, Maryland, United States
  • 2000–2004
    • Johns Hopkins University
      • Department of Chemistry
      Baltimore, Maryland, United States
  • 2003
    • Vrije Universiteit Brussel
      Bruxelles, Brussels Capital, Belgium
  • 1999
    • Australian Institute of Marine Science
      Townsville, Queensland, Australia
  • 1997
    • National Institute of Standards and Technology
      Maryland, United States