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See detailSystems ecology of microbiomes: a new frontier of discovery in microbiology
Wilmes, Paul UL

Scientific Conference (2017, September)

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See detailFrom integrated multi-omics to microbial systems ecology: quo vadis?
Wilmes, Paul UL

Scientific Conference (2017, August)

Detailed reference viewed: 20 (1 UL)
See detailSystems ecology of microbiomes: a new frontier of discovery in microbiology
Wilmes, Paul UL

Presentation (2017, August)

Detailed reference viewed: 20 (0 UL)
See detailSystems ecology of microbiomes: a new frontier of discovery in microbiology
Wilmes, Paul UL

Presentation (2017, August)

Detailed reference viewed: 16 (0 UL)
See detailIntegrated multi-omics for identifying discriminant features in the human microbiome
Wilmes, Paul UL

Scientific Conference (2017, June)

Detailed reference viewed: 18 (2 UL)
See detailUntangling the microbial ecology of anaerobic digestion through integrated multi-omics
Wilmes, Paul UL

Scientific Conference (2017, May)

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See detailSystems Ecology of Microbiomes: A New Frontier of Discovery in Microbiology
Wilmes, Paul UL

Scientific Conference (2017, May)

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See detailColonization and Succession within the Human Gut Microbiome by Archaea, Bacteria, and Microeukaryotes during the First Year of Life
Wampach, Linda UL; Heintz, Anna UL; Hogan, Angela et al

in Frontiers in Microbiology (2017)

Perturbations to the colonization process of the human gastrointestinal tract have been suggested to result in adverse health effects later in life. Although much research has been performed on bacterial ... [more ▼]

Perturbations to the colonization process of the human gastrointestinal tract have been suggested to result in adverse health effects later in life. Although much research has been performed on bacterial colonization and succession, much less is known about the other two domains of life, archaea, and eukaryotes. Here we describe colonization and succession by bacteria, archaea and microeukaryotes during the first year of life (samples collected around days 1, 3, 5, 28, 150, and 365) within the gastrointestinal tract of infants delivered either vaginally or by cesarean section and using a combination of quantitative real-time PCR as well as 16S and 18S rRNA gene amplicon sequencing. Sequences from organisms belonging to all three domains of life were detectable in all of the collected meconium samples. The microeukaryotic community composition fluctuated strongly over time and early diversification was delayed in infants receiving formula milk. Cesarean section-delivered (CSD) infants experienced a delay in colonization and succession, which was observed for all three domains of life. Shifts in prokaryotic succession in CSD infants compared to vaginally delivered (VD) infants were apparent as early as days 3 and 5, which were characterized by increased relative abundances of the genera Streptococcus and Staphylococcus, and a decrease in relative abundance for the genera Bifidobacterium and Bacteroides. Generally, a depletion in Bacteroidetes was detected as early as day 5 postpartum in CSD infants, causing a significantly increased Firmicutes/Bacteroidetes ratio between days 5 and 150 when compared to VD infants. Although the delivery mode appeared to have the strongest influence on differences between the infants, other factors such as a younger gestational age or maternal antibiotics intake likely contributed to the observed patterns as well. Our findings complement previous observations of a delay in colonization and succession of CSD infants, which affects not only bacteria but also archaea and microeukaryotes. This further highlights the need for resolving bacterial, archaeal, and microeukaryotic dynamics in future longitudinal studies of microbial colonization and succession within the neonatal gastrointestinal tract. [less ▲]

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See detailTowards systems ecology of the human gut microbiome
Wilmes, Paul UL

Presentation (2017, March)

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See detailSystems Ecology of Microbiomes: A New Frontier of Discovery in Microbiology
Wilmes, Paul UL

Scientific Conference (2017, March)

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See detailFrom meta-genomics to causality: Understanding the role of colon cancer-associated bacteria in colorectal cancer
Ternes, Dominik UL; Wilmes, Paul UL; Letellier, Elisabeth UL et al

Poster (2017, February 05)

The human gastrointestinal tract is home for trillions of bacteria that influence homeostasis and health in a complex biological system: the gut microbiome. Accumulating evidence suggests that a state of ... [more ▼]

The human gastrointestinal tract is home for trillions of bacteria that influence homeostasis and health in a complex biological system: the gut microbiome. Accumulating evidence suggests that a state of pathological imbalance in the microbiome (dysbiosis) is present in patients suffering from colorectal cancer (CRC). To date, microbiome studies identified specific bacteria being associated with dysbiosis in CRC. Some of these bacteria (e.g. Fusobacteria) directly or indirectly interact with cancer and immune cells of their host. However, current studies only focused on certain microbes in detail, hence, their role in the etiology of the disease remains elusive. Accordingly, my project investigates the role of CRC-associated bacteria in tumor initiation and progression while addressing the question: which and what kind of microbes interact with, favor, or can cause CRC? In a first step, we identified CRC-associated bacteria, enriched at the tumor site of Luxembourgish CRC patients. By using Fusobacterium nucleatum as our study model, we predicted and optimized bacterial growth (media) in silico by using a genome-scale metabolic reconstruction model for a constraint-based modelling approach. Next, we assessed bacterial growth and metabolism in the optimized growth medium by using flow cytometry and mass spectrometry. Finally, we co-cultured the bacteria together with primary patient-derived cultures in the recently developed, microfluidics-based, human-microbial cross-talk model (HuMiX) [1]. As part of our ongoing validations, we infected patient-derived, healthy and cancerous 3D colonic organoids with our bacterial candidate. This workflow enables us to analyze pro-tumorigenic capacities of CRC-associated bacteria on healthy and cancerous colonocytes. It will serve as a promising tool for future analysis of host-microbial interaction mechanisms of various CRC-associated bacteria on a transcriptomic, proteomic, and metabolomic level. [1] Shah P, Fritz JV, Glaab E, Desai MS, Greenhalgh K et al. (2016) A microfluidics-based in vitro model of the gastrointestinal human-microbe interface. Nature communications 7: 11535. [less ▲]

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See detailFrom gut to sludge: how to sustainably manage microbial communities in future
Wilmes, Paul UL

Scientific Conference (2017, February)

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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 detailICoVeR - an interactive visualization tool for verification and refinement of metagenomic bins.
Broeksema, Bertjan; Calusinska, Magdalena; McGee, Fintan et al

in BMC bioinformatics (2017), 18(1), 233

BACKGROUND: Recent advances in high-throughput sequencing allow for much deeper exploitation of natural and engineered microbial communities, and to unravel so-called "microbial dark matter" (microbes ... [more ▼]

BACKGROUND: Recent advances in high-throughput sequencing allow for much deeper exploitation of natural and engineered microbial communities, and to unravel so-called "microbial dark matter" (microbes that until now have evaded cultivation). Metagenomic analyses result in a large number of genomic fragments (contigs) that need to be grouped (binned) in order to reconstruct draft microbial genomes. While several contig binning algorithms have been developed in the past 2 years, they often lack consensus. Furthermore, these software tools typically lack a provision for the visualization of data and bin characteristics. RESULTS: We present ICoVeR, the Interactive Contig-bin Verification and Refinement tool, which allows the visualization of genome bins. More specifically, ICoVeR allows curation of bin assignments based on multiple binning algorithms. Its visualization window is composed of two connected and interactive main views, including a parallel coordinates view and a dimensionality reduction plot. To demonstrate ICoVeR's utility, we used it to refine disparate genome bins automatically generated using MetaBAT, CONCOCT and MyCC for an anaerobic digestion metagenomic (AD microbiome) dataset. Out of 31 refined genome bins, 23 were characterized with higher completeness and lower contamination in comparison to their respective, automatically generated, genome bins. Additionally, to benchmark ICoVeR against a previously validated dataset, we used Sharon's dataset representing an infant gut metagenome. CONCLUSIONS: ICoVeR is an open source software package that allows curation of disparate genome bins generated with automatic binning algorithms. It is freely available under the GPLv3 license at https://git.list.lu/eScience/ICoVeR . The data management and analytical functions of ICoVeR are implemented in R, therefore the software can be easily installed on any system for which R is available. Installation and usage guide together with the example files ready to be visualized are also provided via the project wiki. ICoVeR running instance preloaded with AD microbiome and Sharon's datasets can be accessed via the website. [less ▲]

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See detailIntegrated meta-omic analyses of the gastrointestinal tract microbiome in patients undergoing allogeneic hematopoietic stem cell transplantation.
Kaysen, Anne UL; Heintz, Anna UL; Muller, Emilie UL et al

in Translational Research: the Journal of Laboratory and Clinical Medicine (2017)

In patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), treatment-induced changes to the gastrointestinal tract (GIT) microbiome have been linked to adverse outcomes, most ... [more ▼]

In patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), treatment-induced changes to the gastrointestinal tract (GIT) microbiome have been linked to adverse outcomes, most notably graft-versus-host disease (GvHD). However, it is presently unknown whether this relationship is causal or consequential. Here, we performed an integrated meta-omic analysis to probe deeper into the GIT microbiome changes during allo-HSCT and its accompanying treatments. We used 16S and 18S rRNA gene amplicon sequencing to resolve archaea, bacteria, and eukaryotes within the GIT microbiomes of 16 patients undergoing allo-HSCT for the treatment of hematologic malignancies. These results revealed a major shift in the GIT microbiome after allo-HSCT including a marked reduction in bacterial diversity, accompanied by only limited changes in eukaryotes and archaea. An integrated analysis of metagenomic and metatranscriptomic data was performed on samples collected from a patient before and after allo-HSCT for acute myeloid leukemia. This patient developed severe GvHD, leading to death 9 months after allo-HSCT. In addition to drastically decreased bacterial diversity, the post-treatment microbiome showed a higher overall number and higher expression levels of antibiotic resistance genes (ARGs). One specific Escherichia coli strain causing a paravertebral abscess was linked to GIT dysbiosis, suggesting loss of intestinal barrier integrity. The apparent selection for bacteria expressing ARGs suggests that prophylactic antibiotic administration may adversely affect the overall treatment outcome. We therefore assert that such analyses including information about the selection of pathogenic bacteria expressing ARGs may assist clinicians in "personalizing" regimens for individual patients to improve overall outcomes. [less ▲]

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See detailThe nasal and gut microbiome in Parkinson's disease and idiopathic rapid eye movement sleep behavior disorder.
Heintz, Anna UL; Pandey, Urvashi; Wicke, Tamara et al

in Movement disorders : official journal of the Movement Disorder Society (2017)

BACKGROUND: Increasing evidence connects the gut microbiota and the onset and/or phenotype of Parkinson's disease (PD). Differences in the abundances of specific bacterial taxa have been reported in PD ... [more ▼]

BACKGROUND: Increasing evidence connects the gut microbiota and the onset and/or phenotype of Parkinson's disease (PD). Differences in the abundances of specific bacterial taxa have been reported in PD patients. It is, however, unknown whether these differences can be observed in individuals at high risk, for example, with idiopathic rapid eye movement sleep behavior disorder, a prodromal condition of alpha-synuclein aggregation disorders including PD. OBJECTIVES: To compare microbiota in carefully preserved nasal wash and stool samples of subjects with idiopathic rapid eye movement sleep behavior disorder, manifest PD, and healthy individuals. METHODS: Microbiota of flash-frozen stool and nasal wash samples from 76 PD patients, 21 idiopathic rapid eye movement sleep behavior disorder patients, and 78 healthy controls were assessed by 16S and 18S ribosomal RNA amplicon sequencing. Seventy variables, related to demographics, clinical parameters including nonmotor symptoms, and sample processing, were analyzed in relation to microbiome variability and controlled differential analyses were performed. RESULTS: Differentially abundant gut microbes, such as Akkermansia, were observed in PD, but no strong differences in nasal microbiota. Eighty percent of the differential gut microbes in PD versus healthy controls showed similar trends in idiopathic rapid eye movement sleep behavior disorder, for example, Anaerotruncus and several Bacteroides spp., and correlated with nonmotor symptoms. Metagenomic sequencing of select samples enabled the reconstruction of genomes of so far uncharacterized differentially abundant organisms. CONCLUSION: Our study reveals differential abundances of gut microbial taxa in PD and its prodrome idiopathic rapid eye movement sleep behavior disorder in comparison to the healthy controls, and highlights the potential of metagenomics to identify and characterize microbial taxa, which are enriched or depleted in PD and/or idiopathic rapid eye movement sleep behavior disorder. (c) 2017 International Parkinson and Movement Disorder Society. [less ▲]

Detailed reference viewed: 216 (34 UL)