Showing papers by "Georg Zeller published in 2017"
ETH Zurich1, University of Évry Val d'Essonne2, Centre national de la recherche scientifique3, Institut national de la recherche agronomique4, University of Guelph5, University College Cork6, University of Helsinki7, Wageningen University and Research Centre8, University of British Columbia9, University of Aberdeen10, Waseda University11, University of Tokyo12, Baylor College of Medicine13, Medical University of Graz14, University of Florida15, Okayama University16, Maastricht University17, Statens Serum Institut18, University of Western Ontario19, Shanghai Jiao Tong University20, King's College London21
TL;DR: A standardized DNA extraction method for human fecal samples is recommended, for which transferability across labs was established and which was further benchmarked using a mock community of known composition to improve comparability of human gut microbiome studies and facilitate meta-analyses.
Abstract: Technical variation in metagenomic analysis must be minimized to confidently assess the contributions of microbiota to human health. Here we tested 21 representative DNA extraction protocols on the same fecal samples and quantified differences in observed microbial community composition. We compared them with differences due to library preparation and sample storage, which we contrasted with observed biological variation within the same specimen or within an individual over time. We found that DNA extraction had the largest effect on the outcome of metagenomic analysis. To rank DNA extraction protocols, we considered resulting DNA quantity and quality, and we ascertained biases in estimates of community diversity and the ratio between Gram-positive and Gram-negative bacteria. We recommend a standardized DNA extraction method for human fecal samples, for which transferability across labs was established and which was further benchmarked using a mock community of known composition. Its adoption will improve comparability of human gut microbiome studies and facilitate meta-analyses.
516 citations
TL;DR: A large‐scale survey of population structure in prevalent human gut microbial species, sampled from their natural environment, with a culture‐independent metagenomic approach provides evidence for subspecies in the majority of abundant gut prokaryotes, leading to a better functional and ecological understanding of the human gut microbiome in conjunction with its host.
Abstract: Population genomics of prokaryotes has been studied in depth in only a small number of primarily pathogenic bacteria, as genome sequences of isolates of diverse origin are lacking for most species. Here, we conducted a large-scale survey of population structure in prevalent human gut microbial species, sampled from their natural environment, with a culture-independent metagenomic approach. We examined the variation landscape of 71 species in 2,144 human fecal metagenomes and found that in 44 of these, accounting for 72% of the total assigned microbial abundance, single-nucleotide variation clearly indicates the existence of sub-populations (here termed subspecies). A single subspecies (per species) usually dominates within each host, as expected from ecological theory. At the global scale, geographic distributions of subspecies differ between phyla, with Firmicutes subspecies being significantly more geographically restricted. To investigate the functional significance of the delineated subspecies, we identified genes that consistently distinguish them in a manner that is independent of reference genomes. We further associated these subspecies-specific genes with properties of the microbial community and the host. For example, two of the three Eubacterium rectale subspecies consistently harbor an accessory pro-inflammatory flagellum operon that is associated with lower gut community diversity, higher host BMI, and higher blood fasting insulin levels. Using an additional 676 human oral samples, we further demonstrate the existence of niche specialized subspecies in the different parts of the oral cavity. Taken together, we provide evidence for subspecies in the majority of abundant gut prokaryotes, leading to a better functional and ecological understanding of the human gut microbiome in conjunction with its host.
107 citations
TL;DR: The article summarizes the recent developments, but also limitations and challenges for the development of microbiome-based biomarkers for cancer early detection.
Abstract: The human microbiome - the vast amount of microbes that colonize our body - play an important role in maintaining our health. Changes in microbiome composition have been linked to multiple diseases including cancer. Although mechanisms and causalities of these associations still have to be uncovered, microbiome alterations across various stages of disease can be utilized for novel diagnostic and prognostic tests. Research on biomarkers extracted from the gut microbiome has in particular focused on colorectal cancer, where clinical use is already on the horizon. For example, multiple microbial taxonomic markers such as Fusobacterium nucleatum and other oral pathogens have been identified in human feces with potential for non-invasive diagnostics and prognostics. The article summarizes the recent developments, but also limitations and challenges for the development of microbiome-based biomarkers for cancer early detection.
4 citations