Showing papers by "Georg Zeller published in 2019"
University of Copenhagen1, Lund University2, Molecular Medicine Partnership Unit3, ETH Zurich4, Fudan University5, German Cancer Research Center6, University of São Paulo7, University of Trento8, European Institute of Oncology9, Japan Society for the Promotion of Science10, Tokyo Institute of Technology11, University of Tokyo12, Osaka University13, National Presto Industries14, City University of New York15, National Institutes of Health16, Huntsman Cancer Institute17, University of Southern Denmark18
TL;DR: A meta-analysis of eight geographically and technically diverse fecal shotgun metagenomic studies of colorectal cancer identified a core set of 29 species significantly enriched in CRC metagenomes, establishing globally generalizable, predictive taxonomic and functional microbiome CRC signatures as a basis for future diagnostics.
Abstract: Association studies have linked microbiome alterations with many human diseases. However, they have not always reported consistent results, thereby necessitating cross-study comparisons. Here, a meta-analysis of eight geographically and technically diverse fecal shotgun metagenomic studies of colorectal cancer (CRC, n = 768), which was controlled for several confounders, identified a core set of 29 species significantly enriched in CRC metagenomes (false discovery rate (FDR) < 1 × 10−5). CRC signatures derived from single studies maintained their accuracy in other studies. By training on multiple studies, we improved detection accuracy and disease specificity for CRC. Functional analysis of CRC metagenomes revealed enriched protein and mucin catabolism genes and depleted carbohydrate degradation genes. Moreover, we inferred elevated production of secondary bile acids from CRC metagenomes, suggesting a metabolic link between cancer-associated gut microbes and a fat- and meat-rich diet. Through extensive validations, this meta-analysis firmly establishes globally generalizable, predictive taxonomic and functional microbiome CRC signatures as a basis for future diagnostics. Cross-study analysis defines fecal microbial species associated with colorectal cancer.
615 citations
University of São Paulo1, University of Trento2, European Institute of Oncology3, University of Turin4, Tokyo Institute of Technology5, Japan Society for the Promotion of Science6, University of Tokyo7, Osaka University8, National Presto Industries9, German Cancer Research Center10, Huntsman Cancer Institute11, University of Southern Denmark12, University of Copenhagen13, Virginia Bioinformatics Institute14, City University of New York15
TL;DR: The combined analysis of heterogeneous CRC cohorts identified reproducible microbiome biomarkers and accurate disease-predictive models that can form the basis for clinical prognostic tests and hypothesis-driven mechanistic studies.
Abstract: Several studies have investigated links between the gut microbiome and colorectal cancer (CRC), but questions remain about the replicability of biomarkers across cohorts and populations. We performed a meta-analysis of five publicly available datasets and two new cohorts and validated the findings on two additional cohorts, considering in total 969 fecal metagenomes. Unlike microbiome shifts associated with gastrointestinal syndromes, the gut microbiome in CRC showed reproducibly higher richness than controls (P < 0.01), partially due to expansions of species typically derived from the oral cavity. Meta-analysis of the microbiome functional potential identified gluconeogenesis and the putrefaction and fermentation pathways as being associated with CRC, whereas the stachyose and starch degradation pathways were associated with controls. Predictive microbiome signatures for CRC trained on multiple datasets showed consistently high accuracy in datasets not considered for model training and independent validation cohorts (average area under the curve, 0.84). Pooled analysis of raw metagenomes showed that the choline trimethylamine-lyase gene was overabundant in CRC (P = 0.001), identifying a relationship between microbiome choline metabolism and CRC. The combined analysis of heterogeneous CRC cohorts thus identified reproducible microbiome biomarkers and accurate disease-predictive models that can form the basis for clinical prognostic tests and hypothesis-driven mechanistic studies. Multicohort analysis identifies microbial signatures of colorectal cancer in fecal microbiomes.
478 citations
TL;DR: mOTUs2, an updated and functionally extended profiling tool for microbial abundance, activity and population profiling, shows that mOTUs, which are based on essential housekeeping genes, are demonstrably well-suited for quantification of basal transcriptional activity of community members.
Abstract: Metagenomic sequencing has greatly improved our ability to profile the composition of environmental and host-associated microbial communities. However, the dependency of most methods on reference genomes, which are currently unavailable for a substantial fraction of microbial species, introduces estimation biases. We present an updated and functionally extended tool based on universal (i.e., reference-independent), phylogenetic marker gene (MG)-based operational taxonomic units (mOTUs) enabling the profiling of >7700 microbial species. As more than 30% of them could not previously be quantified at this taxonomic resolution, relative abundance estimates based on mOTUs are more accurate compared to other methods. As a new feature, we show that mOTUs, which are based on essential housekeeping genes, are demonstrably well-suited for quantification of basal transcriptional activity of community members. Furthermore, single nucleotide variation profiles estimated using mOTUs reflect those from whole genomes, which allows for comparing microbial strain populations (e.g., across different human body sites).
262 citations
TL;DR: Evidence is found for a vast majority of oral species to be transferable, with increased levels of transmission in colorectal cancer and rheumatoid arthritis patients and, more generally, for species described as opportunistic pathogens.
Abstract: The gastrointestinal tract is abundantly colonized by microbes, yet the translocation of oral species to the intestine is considered a rare aberrant event, and a hallmark of disease. By studying salivary and fecal microbial strain populations of 310 species in 470 individuals from five countries, we found that transmission to, and subsequent colonization of, the large intestine by oral microbes is common and extensive among healthy individuals. We found evidence for a vast majority of oral species to be transferable, with increased levels of transmission in colorectal cancer and rheumatoid arthritis patients and, more generally, for species described as opportunistic pathogens. This establishes the oral cavity as an endogenous reservoir for gut microbial strains, and oral-fecal transmission as an important process that shapes the gastrointestinal microbiome in health and disease.
253 citations
Swiss Institute of Bioinformatics1, French Alternative Energies and Atomic Energy Commission2, Technical University of Madrid3, Fudan University4, Ohio State University5, Laval University6, IFREMER7, Spanish National Research Council8, Hewlett-Packard9, University of Paris10, École Normale Supérieure11, Shirshov Institute of Oceanology12, University of Maine13, European Bioinformatics Institute14, Massachusetts Institute of Technology15, Bigelow Laboratory For Ocean Sciences16
TL;DR: The relative contribution of gene expression changes to be significantly lower in polar than in non-polar waters and it is hypothesized that in polar regions, alterations in community activity in response to ocean warming will be driven more strongly by changes in organismal composition than by gene regulatory mechanisms.
217 citations
TL;DR: The presented proGenomes2 provides threefold more genomes, enhanced habitat annotations, updated taxonomic and functional annotation and improved linkage to the NCBI BioSample database.
Abstract: Microbiology depends on the availability of annotated microbial genomes for many applications. Comparative genomics approaches have been a major advance, but consistent and accurate annotations of genomes can be hard to obtain. In addition, newer concepts such as the pan-genome concept are still being implemented to help answer biological questions. Hence, we present proGenomes2, which provides 87 920 high-quality genomes in a user-friendly and interactive manner. Genome sequences and annotations can be retrieved individually or by taxonomic clade. Every genome in the database has been assigned to a species cluster and most genomes could be accurately assigned to one or multiple habitats. In addition, general functional annotations and specific annotations of antibiotic resistance genes and single nucleotide variants are provided. In short, proGenomes2 provides threefold more genomes, enhanced habitat annotations, updated taxonomic and functional annotation and improved linkage to the NCBI BioSample database. The database is available at http://progenomes.embl.de/.
55 citations
TL;DR: Findings were inconsistent and based on studies with high to unclear risk of bias, and small sample sizes, well-powered trials with repeated blood measurements of SCFAs are required.
30 citations
University of São Paulo1, University of Trento2, European Institute of Oncology3, University of Turin4, Japan Society for the Promotion of Science5, Tokyo Institute of Technology6, University of Tokyo7, Osaka University8, National Presto Industries9, German Cancer Research Center10, Huntsman Cancer Institute11, University of Copenhagen12, University of Southern Denmark13, Virginia Bioinformatics Institute14, City University of New York15
TL;DR: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
4 citations