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See detailIndividual factors and beliefs determining COVID-19 vaccination willingness
Pauly, Laure UL; Klee, Matthias UL; Paccoud, Ivana UL et al

Poster (2022, April)

Background: High vaccination coverage rates are necessary to reduce infections and transmissions of the SARS-CoV-2 virus causing COVID-19 and to allow successful mitigation of the current pandemic. To ... [more ▼]

Background: High vaccination coverage rates are necessary to reduce infections and transmissions of the SARS-CoV-2 virus causing COVID-19 and to allow successful mitigation of the current pandemic. To date, we are still lacking information to explain the hesitancy in Luxembourg towards uptake of the available COVID-19 vaccines. The present study explored motivations for and against vaccination in a population-representative sample of residents across Luxembourg to identify hesitant groups and develop strategies to increase population immunity against SARS-CoV-2. Methods: In the framework of the nationwide, representative longitudinal CON-VINCE study, a sample of 1589 respondents (49.6% women, 84.3% Luxembourg nationality) ranging from 18-84 years, participated in the survey in spring 2021. The protocol of the CON-VINCE study has been described in detail elsewhere (Snoeck et al. 2020). Results: 52% of the respondents had at least partial vaccination at time of assessment between April to June 2021. The most common reasons for vaccination of those willing to be vaccinated (81.2%) were altruistic motivations. Prevalent reasons against vaccination for those undecided (8.7%) or reluctant (10.2%) to be vaccinated were that the vaccine had not been tested sufficiently and the fear of long-term vaccine side effects. Only very few of the vaccination-hesitant or -reluctant respondents reported that they did not believe in vaccination in general. Conclusion: The present study identified motivations for and against COVID-19 vaccination and determined demographic and socio-economic factors associated with vaccination willingness. To increase vaccination rates, public health communication needs to target those unsure or unwilling to be vaccinated. We will continue to study the vaccination uptake in the Luxembourg population, as CON-VINCE is now part of the H2020-funded international ORCHESTRA project (https://orchestra-cohort.eu), research into comparing these results on a Pan-European level. [less ▲]

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See detailDeterminants of Self-Stigma in People with Parkinson's Disease: A Mixed Methods Scoping Review
Hanff, Anne-Marie UL; Leist, Anja UL; Fritz, Joëlle UL et al

in Journal of Parkinson's Disease (2021)

Background: Self-stigma in people with Parkinson's disease (PD) can substantially impact quality of life and possibilities for social participation. An integrative analysis of determinants of self-stigma ... [more ▼]

Background: Self-stigma in people with Parkinson's disease (PD) can substantially impact quality of life and possibilities for social participation. An integrative analysis of determinants of self-stigma has been lacking. Objective: We sought to explore which complementary insights from qualitative and quantitative studies, as well as from expert consultation, could be gained. Methods: An established mixed methods study design was employed to first conduct a mixed methods scoping review of published qualitative and quantitative literature, and then consult with experts to arrive at an exhaustive list of determinants of self-stigma after a thematic synthesis. Results: A total of 87 unique determinants of self-stigma were identified. Quantitative studies and expert consultations mainly identified personal determinants of people with self-stigma (e.g., age, anxiety, or apathy). In contrast, qualitative studies identified social situations associated with self-stigma (e.g., joint meals of people with typical PD with others). Notably, self-stigma of people with PD was found to be particularly salient in unfamiliar places, at the working place or in contact with people without PD. Across methods, cognitive impairment, tremor, and abnormal walk and unsteady gait, respectively, were associated with self-stigma. Conclusion: The mixed method study design yielded complementary insights, but also factors commonly associated with self-stigma across methods. Future prioritization exercises may gain further insights into self-stigma of people with PD. Facilitating social encounters by both addressing needs of affected people and raising knowledge and public awareness may improve quality of life in people with PD [less ▲]

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See detailWhich demographic and socio-economic factors are associated with vaccination willingness and beliefs towards vaccination? Rapid report with first results
Leist, Anja UL; Klee, Matthias UL; Paccoud, Ivana UL et al

Report (2021)

In the framework of the CoVaLux project on vaccination and long COVID in Luxembourg, the project “Socio-economic determinants of long COVID and vaccination, and economic consequences with focus on labour ... [more ▼]

In the framework of the CoVaLux project on vaccination and long COVID in Luxembourg, the project “Socio-economic determinants of long COVID and vaccination, and economic consequences with focus on labour market and health care” aims to triangulate evidence from different data sources such as social security and general population data, the national cohort CON-VINCE as well as national health surveys. We seek to arrive at robust assessments of how socio-economic determinants shape vaccination willingness, occurrence, severity and persistence of long COVID, and economic consequences of long COVID in Luxembourg. [less ▲]

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See detailPersistence of birth mode-dependent effects on gut microbiome composition, immune system stimulation and antimicrobial resistance during the first year of life
Busi, Susheel Bhanu UL; de Nies, Laura UL; Habier, Janine UL et al

in ISME Communications (2021)

Caesarean section delivery (CSD) disrupts mother-to-neonate transmission of specific microbial strains and functional repertoires as well as linked immune system priming. Here we investigate whether ... [more ▼]

Caesarean section delivery (CSD) disrupts mother-to-neonate transmission of specific microbial strains and functional repertoires as well as linked immune system priming. Here we investigate whether differences in microbiome composition and impacts on host physiology persist at 1 year of age. We perform high-resolution, quantitative metagenomic analyses of the gut microbiomes of infants born by vaginal delivery (VD) or by CSD, from immediately after birth through to 1 year of life. Several microbial populations show distinct enrichments in CSD-born infants at 1 year of age including strains of Bacteroides caccae, Bifidobacterium bifidum and Ruminococcus gnavus, whereas others are present at higher levels in the VD group including Faecalibacterium prausnitizii, Bifidobacterium breve and Bifidobacterium kashiwanohense. The stimulation of healthy donor-derived primary human immune cells with LPS isolated from neonatal stool samples results in higher levels of tumour necrosis factor alpha (TNF-α) in the case of CSD extracts over time, compared to extracts from VD infants for which no such changes were observed during the first year of life. Functional analyses of the VD metagenomes at 1 year of age demonstrate a significant increase in the biosynthesis of the natural antibiotics, carbapenem and phenazine. Concurrently, we find antimicrobial resistance (AMR) genes against several classes of antibiotics in both VD and CSD. The abundance of AMR genes against synthetic (including semi-synthetic) agents such as phenicol, pleuromutilin and diaminopyrimidine are increased in CSD children at day 5 after birth. In addition, we find that mobile genetic elements, including phages, encode AMR genes such as glycopeptide, diaminopyrimidine and multidrug resistance genes. Our results demonstrate persistent effects at 1 year of life resulting from birth mode-dependent differences in earliest gut microbiome colonisation. [less ▲]

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See detailPrevalence of SARS-CoV-2 infection in the Luxembourgish population: the CON-VINCE study.
Snoeck, Chantal J.; Vaillant, Michel; Abdelrahman, Tamir et al

E-print/Working paper (2020)

BACKGROUND: After the World Health Organization declared the outbreak of coronavirus disease to be a public health emergency of international concern on January 30, 2020, the first SARS-CoV-2 infection ... [more ▼]

BACKGROUND: After the World Health Organization declared the outbreak of coronavirus disease to be a public health emergency of international concern on January 30, 2020, the first SARS-CoV-2 infection was detected in Luxembourg on February 29, 2020. Representative population-based data, including asymptomatic individuals for assessing the viral spread and immune response were, however, lacking worldwide. METHODS: Using a panel-based method, we implemented a representative sample of the Luxembourgish population based on age, gender and residency for testing for SARS-CoV-2 infection and antibody status in order to define prevalence irrespective of clinical symptoms. Participants were contacted via email to fill an online questionnaire before biosampling at local laboratories. All participants provided information related to clinical symptoms, epidemiology, socioeconomic and psychological assessments and underwent biosampling, rRT-PCR testing and serology for SARS-CoV-2. RESULTS: We included a total of 1862 individuals in our representative sample of the general Luxembourgish population. Of these, 5 individuals had a current positive result for infection with SARS-CoV-2 based on rRT-PCR. Four of these individuals were oligosymptomatic and one was asymptomatic. Overall we found a positive IgG antibody status in 35 individuals (1.97%), of which 11 reported to be tested positive by rRT-PCR for SARS-CoV-2 previously and showed in addition their IgG positive status also a positive status for IgA. Our data indicate a prevalence of 0.3% for active SARS-CoV-2 infection and an infection rate of 2.15% in the Luxembourgish population between 18 and 79 years of age. CONCLUSIONS: Luxembourgish residents show a low rate of acute infections after 7 weeks of confinement and present with an antibody profile indicative of a more recent immune response to SARS-CoV-2. All infected individuals were oligo- or asymptomatic. Bi-weekly follow-up visits over the next 2 months will inform about the viral spread by a- and oligosymptomatic carriers and the individual changes in the immune profile.Competing Interest StatementThe authors have declared no competing interest.Clinical TrialNCT04379297Funding StatementThe CON-VINCE Study is funded by the Research Fund Luxembourg (FNR; CON-VINCE) and the André Losch Foundation (Luxembourg).Author DeclarationsAll relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript.YesAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesDue to ethical concerns, supporting data cannot be made openly available. [less ▲]

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See detailProgramme Démence Prévention (pdp ): A Nation-Wide Programme for Dementia Prevention in Luxembourg
Schröder, Valerie UL; Kaysen, Anne UL; Fritz, Joëlle UL et al

Poster (2020, April)

Objectives: To implement a multi-year nation-wide programme, by the means of a personalised lifestyle intervention, to prevent or to delay cognitive decline that can contribute to development of dementia ... [more ▼]

Objectives: To implement a multi-year nation-wide programme, by the means of a personalised lifestyle intervention, to prevent or to delay cognitive decline that can contribute to development of dementia in Luxembourg. Methods: Participants with mild cognitive impairment, referred to the programme by their treating physician, undergo an extensive cognitive evaluation by a neuropsychologist on relevant neuropsychological domains as well as a structured dementia risk factor assessment. Based on these assessments, individualised lifestyle interventions are offered by diverse national partners involved in the programme, thus filling a gap of not yet reimbursed services in the Luxemburgish healthcare system. After the personalised lifestyle interventions, each participant will undergo a neuropsychological follow-up in order to re-evaluate his/her health status in terms of cognition. Results: We established a participant-centred national network by presenting the programme on many outreach events and efficient stakeholder communication. The network raises the awareness of dementia prevention in the Luxembourgish population, fosters interdisciplinary communication between individual medical and non-medical healthcare professionals and allows for a successful recruitment of the target population. Moreover, we collect information about adherence to the suggested lifestyle changes, as well as the effectiveness of our interventions in reducing risk factors contributing to the onset of dementia. Conclusions: We provide evidence for the feasibility of the implementation of a nation-wide dementia prevention programme including diverse partners offering personalised lifestyle interventions, which are easily transferrable to other countries. Future results from this programme may also help to integrate prevention interventions into the regular healthcare system. [less ▲]

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See detailIntegrated In Vitro and In Silico Modeling Delineates the Molecular Effects of a Synbiotic Regimen on Colorectal-Cancer-Derived Cells
Greenhalgh, Kacy UL; Ramiro Garcia, Javier UL; Heinken et al

in Cell Reports (2019), 27

By modulating the human gut microbiome, prebiotics and probiotics (combinations of which are called synbiotics) may be used to treat diseases such as colorectal cancer (CRC). Methodological limitations ... [more ▼]

By modulating the human gut microbiome, prebiotics and probiotics (combinations of which are called synbiotics) may be used to treat diseases such as colorectal cancer (CRC). Methodological limitations have prevented determining the potential combina- torial mechanisms of action of such regimens. We expanded our HuMiX gut-on-a-chip model to co-culture CRC-derived epithelial cells with a model probiotic under a simulated prebiotic regimen, and we integrated the multi-omic results with in silico metabolic modeling. In contrast to individual prebi- otic or probiotic treatments, the synbiotic regimen caused downregulation of genes involved in procarci- nogenic pathways and drug resistance, and reduced levels of the oncometabolite lactate. Distinct ratios of organic and short-chain fatty acids were produced during the simulated regimens. Treatment of primary CRC-derived cells with a molecular cocktail reflecting the synbiotic regimen attenuated self-renewal ca- pacity. Our integrated approach demonstrates the potential of modeling for rationally formulating synbi- otics-based treatments in the future. [less ▲]

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See detailThe RNA Complement of Outer Membrane Vesicles From Salmonella enterica Serovar Typhimurium Under Distinct Culture Conditions
Malabirade, Antoine UL; Habier, Janine UL; Heintz-Buschart, Anna et al

in Frontiers in Microbiology (2018), 9

Bacterial outer membrane vesicles (OMVs), as well as OMV-associated small RNAs, have been demonstrated to play a role in host–pathogen interactions. The presence of larger RNA transcripts in OMVs has been ... [more ▼]

Bacterial outer membrane vesicles (OMVs), as well as OMV-associated small RNAs, have been demonstrated to play a role in host–pathogen interactions. The presence of larger RNA transcripts in OMVs has been less studied and their potential role in host–pathogen interactions remains largely unknown. Here we analyze RNA from OMVs secreted by Salmonella enterica serovar Typhimurium (S. Typhimurium) cultured under different conditions, which mimic host–pathogen interactions. S. Typhimurium was grown to exponential and stationary growth phases in minimal growth control medium (phosphate-carbon-nitrogen, PCN), as well as in acidic and phosphate-depleted PCN, comparable to the macrophage environment and inducing therefore the expression of Salmonella pathogenicity island 2 (SPI-2) genes. Moreover, Salmonella pathogenicity island 1 (SPI-1), which is required for virulence during the intestinal phase of infection, was induced by culturing S. Typhimurium to the stationary phase in Lysogeny Broth (LB). For each condition, we identified OMV-associated RNAs that are enriched in the extracellular environment relative to the intracellular space. All RNA classes could be observed, but a vast majority of rRNA was exported in all conditions in variable proportions with a notable decrease in LB SPI-1 inducing media. Several mRNAs and ncRNAs were specifically enriched in/on OMVs dependent on the growth conditions. Important to note is that some RNAs showed identical read coverage profiles intracellularly and extracellularly, whereas distinct coverage patterns were observed for other transcripts, suggesting a specific processing or degradation. Moreover, PCR experiments confirmed that distinct RNAs were present in or on OMVs as full-length transcripts (IsrB-1/2; IsrA; ffs; SsrS; CsrC; pSLT035; 10Sa; rnpB; STM0277; sseB; STM0972; STM2606), whereas others seemed to be rather present in a processed or degraded form. Finally, we show by a digestion protection assay that OMVs are able to prevent enzymatic degradation of given full-length transcripts (SsrS, CsrC, 10Sa, and rnpB). In summary, we show that OMV-associated RNA is clearly different in distinct culture conditions and that at least a fraction of the extracellular RNA is associated as a full-length transcripts with OMVs, indicating that some RNAs are protected by OMVs and thereby leaving open the possibility that those might be functionally active. [less ▲]

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See detailSmall RNA profiling of low biomass samples: identification and removal of contaminants
Heintz-Buschart, Anna; Yusuf, Dilmurat; Kaysen, Anne UL et al

in BMC Biology (2018), 16(52),

Background: Sequencing-based analyses of low-biomass samples are known to be prone to misinterpretation due to the potential presence of contaminating molecules derived from laboratory reagents and ... [more ▼]

Background: Sequencing-based analyses of low-biomass samples are known to be prone to misinterpretation due to the potential presence of contaminating molecules derived from laboratory reagents and environments. DNA contamination has been previously reported, however contamination with RNA is usually considered to be unlikely due to its inherent instability. Small RNAs (sRNAs) identified in tissues and bodily fluids such as blood plasma, have implications for physiology and pathology, and therefore the potential to act as disease biomarkers. Thus, the possibility for RNA contaminants demands a careful evaluation. Results: Here we report the presence of small RNA contaminants in widely used microRNA extraction kits and propose an approach for their depletion. We sequenced sRNAs extracted from human plasma samples and detected important levels of non-human (exogenous) sequences whose source could be traced to the microRNA extraction columns through a careful qPCR-based analysis of several laboratory reagents. Furthermore, we also detected the presence of artefactual sequences related to these contaminants in a range of published datasets, arguing for a re-evaluation of reports suggesting the presence of exogenous RNAs of microbial and dietary origins in blood plasma. To avoid artefacts in future experiments, we also devise several protocols of contaminant RNAs, define minimal amounts of starting material for artefact-free analyses, and confirm the reduction of contaminant levels for identification of bona fide sequences using ‘ultra-clean’ extraction kits. Conclusion: This is the first report of the presence of RNA molecules as contaminants in RNA extraction kits. The described protocols should be applied in the future to avoid confounding sRNA studies. [less ▲]

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See detailExtraction and Analysis of RNA Isolated from Pure Bacteria-Derived Outer Membrane Vesicles
Habier, Janine UL; May, Patrick UL; Heintz-Buschart, Anna et al

in Arluison, Véronique; Valverde, Claudio Valverde (Eds.) Bacterial Regulatory RNA (2018)

Outer membrane vesicles (OMVs) are released by commensal as well as pathogenic Gram-negative bacteria. These vesicles contain numerous bacterial components, such as proteins, peptidoglycans ... [more ▼]

Outer membrane vesicles (OMVs) are released by commensal as well as pathogenic Gram-negative bacteria. These vesicles contain numerous bacterial components, such as proteins, peptidoglycans, lipopolysaccharides, DNA, and RNA. To examine if OMV-associated RNA molecules are bacterial degradation products and/or are functionally active, it is necessary to extract RNA from pure OMVs for subsequent analysis. Therefore, we describe here an isolation method of ultrapure OMVs and the subsequent extraction of RNA and basic steps of RNA-Seq analysis. Bacterial culture, extracellular supernatant concentration, OMV purification, and the subsequent RNA extraction out of OMVs are described. Specific pitfalls within the protocol and RNA contamination sources are highlighted. [less ▲]

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See detailIsolation of nucleic acids from low biomass samples: detection and removal of sRNA contaminants
Heintz-Buschart, Anna; Yusuf, Dilmurat; Kaysen, Anne UL et al

E-print/Working paper (2017)

Sequencing-based analyses of low-biomass samples are known to be prone to misinterpretation due to the potential presence of contaminating molecules derived from laboratory reagents and environments. Due ... [more ▼]

Sequencing-based analyses of low-biomass samples are known to be prone to misinterpretation due to the potential presence of contaminating molecules derived from laboratory reagents and environments. Due to its inherent instability, contamination with RNA is usually considered to be unlikely. Here we report the presence of small RNA (sRNA) contaminants in widely used microRNA extraction kits and means for their depletion. Sequencing of sRNAs extracted from human plasma samples was performed and significant levels of non-human (exogenous) sequences were detected. The source of the most abundant of these sequences could be traced to the microRNA extraction columns by qPCR-based analysis of laboratory reagents. The presence of artefactual sequences originating from the confirmed contaminants were furthermore replicated in a range of published datasets. To avoid artefacts in future experiments, several protocols for the removal of the contaminants were elaborated, minimal amounts of starting material for artefact-free analyses were defined, and the reduction of contaminant levels for identification of bona fide sequences using 'ultra-clean' extraction kits was confirmed. In conclusion, this is the first report of the presence of RNA molecules as contaminants in laboratory reagents. The described protocols should be applied in the future to avoid confounding sRNA studies. [less ▲]

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See detailEngineering Solutions for Representative Models of the Gastrointestinal Human-Microbe Interface
Mac Giolla Eain, Marc UL; Baginska, Joanna UL; Greenhalgh, Kacy UL et al

in Engineering (2017)

Host-microbe interactions at the gastrointestinal interface have emerged as a key component in the governance of human health and disease. Advances in micro-physiological systems are providing researchers ... [more ▼]

Host-microbe interactions at the gastrointestinal interface have emerged as a key component in the governance of human health and disease. Advances in micro-physiological systems are providing researchers with unprecedented access and insights into this complex relationship. These systems combine the benefits of microengineering, microfluidics, and cell culture in a bid to recreate the environmental conditions prevalent in the human gut. Here we present the human-microbial cross talk (HuMiX) platform, one such system that leverages this multidisciplinary approach to provide a representative in vitro model of the human gastrointestinal interface. HuMiX presents a novel and robust means to study the molecular interactions at the host-microbe interface. We summarize our proof-of-concept results obtained using the platform and highlight its potential to greatly enhance our understanding of host-microbe interactions with a potential to greatly impact the pharmaceutical, food, nutrition, and healthcare industries in the future. A number of key questions and challenges facing these technologies are also discussed. [less ▲]

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See detailGene Regulatory Network Inference of Immunoresponsive Gene 1 (IRG1) Identifies Interferon Regulatory Factor 1 (IRF1) as Its Transcriptional Regulator in Mammalian Macrophages
Antony, Paul UL; Tallam, Aravind UL; Perumal, Thanneer Malai UL et al

in PLoS ONE (2016)

Immunoresponsive gene 1 (IRG1) is one of the highest induced genes in macrophages under pro-inflammatory conditions. Its function has been recently described: it codes for immune-responsive gene 1 protein ... [more ▼]

Immunoresponsive gene 1 (IRG1) is one of the highest induced genes in macrophages under pro-inflammatory conditions. Its function has been recently described: it codes for immune-responsive gene 1 protein/cis-aconitic acid decarboxylase (IRG1/CAD), an enzyme catalysing the production of itaconic acid from cis-aconitic acid, a tricarboxylic acid (TCA) cycle intermediate. Itaconic acid possesses specific antimicrobial properties inhibiting isocitrate lyase, the first enzyme of the glyoxylate shunt, an anaplerotic pathway that bypasses the TCA cycle and enables bacteria to survive on limited carbon conditions. To elucidate the mechanisms underlying itaconic acid production through IRG1 induction in macrophages, we examined the transcriptional regulation of IRG1. To this end, we studied IRG1 expression in human immune cells under different inflammatory stimuli, such as TNFα and IFNγ, in addition to lipopolysaccharides. Under these conditions, as previously shown in mouse macrophages, IRG1/CAD accumulates in mitochondria. Furthermore, using literature information and transcription factor prediction models, we re-constructed raw gene regulatory networks (GRNs) for IRG1 in mouse and human macrophages. We further implemented a contextualization algorithm that relies on genome-wide gene expression data to infer putative cell type-specific gene regulatory interactions in mouse and human macrophages, which allowed us to predict potential transcriptional regulators of IRG1. Among the computationally identified regulators, siRNA-mediated gene silencing of interferon regulatory factor 1 (IRF1) in macrophages significantly decreased the expression of IRG1/CAD at the gene and protein level, which correlated with a reduced production of itaconic acid. Using a synergistic approach of both computational and experimental methods, we here shed more light on the transcriptional machinery of IRG1 expression and could pave the way to therapeutic approaches targeting itaconic acid levels. [less ▲]

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See detailA microfluidics-based in vitro model of the gastrointestinal human-microbe interface.
Shah, Pranjul UL; Fritz, Joëlle UL; Glaab, Enrico UL et al

in Nature communications (2016), 7

Changes in the human gastrointestinal microbiome are associated with several diseases. To infer causality, experiments in representative models are essential, but widely used animal models exhibit ... [more ▼]

Changes in the human gastrointestinal microbiome are associated with several diseases. To infer causality, experiments in representative models are essential, but widely used animal models exhibit limitations. Here we present a modular, microfluidics-based model (HuMiX, human-microbial crosstalk), which allows co-culture of human and microbial cells under conditions representative of the gastrointestinal human-microbe interface. We demonstrate the ability of HuMiX to recapitulate in vivo transcriptional, metabolic and immunological responses in human intestinal epithelial cells following their co-culture with the commensal Lactobacillus rhamnosus GG (LGG) grown under anaerobic conditions. In addition, we show that the co-culture of human epithelial cells with the obligate anaerobe Bacteroides caccae and LGG results in a transcriptional response, which is distinct from that of a co-culture solely comprising LGG. HuMiX facilitates investigations of host-microbe molecular interactions and provides insights into a range of fundamental research questions linking the gastrointestinal microbiome to human health and disease. [less ▲]

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See detailSources and Functions of Extracellular Small RNAs in Human Circulation.
Fritz, Joëlle UL; Heintz, Anna UL; Ghosal, Anubrata et al

in Annual review of nutrition (2016)

Various biotypes of endogenous small RNAs (sRNAs) have been detected in human circulation, including microRNAs, transfer RNAs, ribosomal RNA, and yRNA fragments. These extracellular sRNAs (ex-sRNAs) are ... [more ▼]

Various biotypes of endogenous small RNAs (sRNAs) have been detected in human circulation, including microRNAs, transfer RNAs, ribosomal RNA, and yRNA fragments. These extracellular sRNAs (ex-sRNAs) are packaged and secreted by many different cell types. Ex-sRNAs exhibit differences in abundance in several disease states and have, therefore, been proposed for use as effective biomarkers. Furthermore, exosome-borne ex-sRNAs have been reported to elicit physiological responses in acceptor cells. Exogenous ex-sRNAs derived from diet (most prominently from plants) and microorganisms have also been reported in human blood. Essential issues that remain to be conclusively addressed concern the (a) presence and sources of exogenous ex-sRNAs in human bodily fluids, (b) detection and measurement of ex-sRNAs in human circulation, (c) selectivity of ex-sRNA export and import, (d) sensitivity and specificity of ex-sRNA delivery to cellular targets, and (e) cell-, tissue-, organ-, and organism-wide impacts of ex-sRNA-mediated cell-to-cell communication. We survey the present state of knowledge of most of these issues in this review. Expected final online publication date for the Annual Review of Nutrition Volume 36 is July 17, 2016. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates. [less ▲]

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See detailThe extracellular RNA complement of Escherichia coli
Ghosal, Anubrata UL; Upadhyaya, Bimal Babu UL; Fritz, Joëlle UL et al

in MicrobiologyOpen (2015)

he secretion of biomolecules into the extracellular milieu is a common and well-conserved phenomenon in biology. In bacteria, secreted biomolecules are not only involved in intra-species communication but ... [more ▼]

he secretion of biomolecules into the extracellular milieu is a common and well-conserved phenomenon in biology. In bacteria, secreted biomolecules are not only involved in intra-species communication but they also play roles in inter-kingdom exchanges and pathogenicity. To date, released products, such as small molecules, DNA, peptides, and proteins, have been well studied in bacte- ria. However, the bacterial extracellular RNA complement has so far not been comprehensively characterized. Here, we have analyzed, using a combination of physical characterization and high-throughput sequencing, the extracellular RNA complement of both outer membrane vesicle (OMV)-associated and OMV-free RNA of the enteric Gram-negative model bacterium Escherichia coli K-12 substrain MG1655 and have compared it to its intracellular RNA comple- ment. Our results demonstrate that a large part of the extracellular RNA com- plement is in the size range between 15 and 40 nucleotides and is derived from specific intracellular RNAs. Furthermore, RNA is associated with OMVs and the relative abundances of RNA biotypes in the intracellular, OMV and OMV- free fractions are distinct. Apart from rRNA fragments, a significant portion of the extracellular RNA complement is composed of specific cleavage products of functionally important structural noncoding RNAs, including tRNAs, 4.5S RNA, 6S RNA, and tmRNA. In addition, the extracellular RNA pool includes RNA biotypes from cryptic prophages, intergenic, and coding regions, of which some are so far uncharacterised, for example, transcripts mapping to the fimA- fimL and ves-spy intergenic regions. Our study provides the first detailed char- acterization of the extracellular RNA complement of the enteric model bacte- rium E. coli. Analogous to findings in eukaryotes, our results suggest the selective export of specific RNA biotypes by E. coli, which in turn indicates a potential role for extracellular bacterial RNAs in intercellular communication. [less ▲]

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See detailHuMiX: A MICROFLUIDICS-BASED IN VITRO CO-CULTURE DEVICE FOR INVESTIGATING HOST-MICROBE INTERACTIONS
Wilmes, Paul UL; estes, matt; zenhausern, frederic et al

Scientific Conference (2014, October 30)

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