New insights from uncultivated genomes of the global human gut microbiome

Published on Mar 13, 2019in Nature42.778
· DOI :10.1038/S41586-019-1058-X
Stephen Nayfach18
Estimated H-index: 18
(LBNL: Lawrence Berkeley National Laboratory),
Zhou Jason Shi3
Estimated H-index: 3
(Gladstone Institutes)
+ 2 AuthorsNikos C. Kyrpides100
Estimated H-index: 100
(LBNL: Lawrence Berkeley National Laboratory)
The genome sequences of many species of the human gut microbiome remain unknown, largely owing to challenges in cultivating microorganisms under laboratory conditions. Here we address this problem by reconstructing 60,664 draft prokaryotic genomes from 3,810 faecal metagenomes, from geographically and phenotypically diverse humans. These genomes provide reference points for 2,058 newly identified species-level operational taxonomic units (OTUs), which represents a 50% increase over the previously known phylogenetic diversity of sequenced gut bacteria. On average, the newly identified OTUs comprise 33% of richness and 28% of species abundance per individual, and are enriched in humans from rural populations. A meta-analysis of clinical gut-microbiome studies pinpointed numerous disease associations for the newly identified OTUs, which have the potential to improve predictive models. Finally, our analysis revealed that uncultured gut species have undergone genome reduction that has resulted in the loss of certain biosynthetic pathways, which may offer clues for improving cultivation strategies in the future.
Figures & Tables
📖 Papers frequently viewed together
18 Authors (Edoardo Pasolli, ..., Nicola Segata)
478 Citations
1,125 Citations
341 Citations
#1Alexandre Almeida (EMBL-EBI: European Bioinformatics Institute)H-Index: 15
#2Alex L. Mitchell (EMBL-EBI: European Bioinformatics Institute)H-Index: 28
Last. Robert D. Finn (EMBL-EBI: European Bioinformatics Institute)H-Index: 61
view all 8 authors...
The composition of the human gut microbiota is linked to health and disease, but knowledge of individual microbial species is needed to decipher their biological roles. Despite extensive culturing and sequencing efforts, the complete bacterial repertoire of the human gut microbiota remains undefined. Here we identify 1,952 uncultured candidate bacterial species by reconstructing 92,143 metagenome-assembled genomes from 11,850 human gut microbiomes. These uncultured genomes substantially expand t...
395 CitationsSource
#1Samuel C. Forster (Monash University, Clayton campus)H-Index: 23
#2Nitin KumarH-Index: 18
Last. Trevor D. LawleyH-Index: 55
view all 17 authors...
Understanding gut microbiome functions requires cultivated bacteria for experimental validation and reference bacterial genome sequences to interpret metagenome datasets and guide functional analyses. We present the Human Gastrointestinal Bacteria Culture Collection (HBC), a comprehensive set of 737 whole-genome-sequenced bacterial isolates, representing 273 species (105 novel species) from 31 families found in the human gastrointestinal microbiota. The HBC increases the number of bacterial geno...
195 CitationsSource
#1Yuanqiang Zou (UCPH: University of Copenhagen)H-Index: 4
#2Wenbin XueH-Index: 4
Last. Liang XiaoH-Index: 20
view all 31 authors...
Reference genomes are essential for metagenomic analyses and functional characterization of the human gut microbiota. We present the Culturable Genome Reference (CGR), a collection of 1,520 nonredundant, high-quality draft genomes generated from >6,000 bacteria cultivated from fecal samples of healthy humans. Of the 1,520 genomes, which were chosen to cover all major bacterial phyla and genera in the human gut, 264 are not represented in existing reference genome catalogs. We show that this incr...
181 CitationsSource
#1Edoardo Pasolli (University of Trento)H-Index: 29
#2Francesco Asnicar (University of Trento)H-Index: 21
Last. Nicola Segata (University of Trento)H-Index: 61
view all 18 authors...
Summary The body-wide human microbiome plays a role in health, but its full diversity remains uncharacterized, particularly outside of the gut and in international populations. We leveraged 9,428 metagenomes to reconstruct 154,723 microbial genomes (45% of high quality) spanning body sites, ages, countries, and lifestyles. We recapitulated 4,930 species-level genome bins (SGBs), 77% without genomes in public repositories (unknown SGBs [uSGBs]). uSGBs are prevalent (in 93% of well-assembled sampl...
478 CitationsSource
#1I-Min A. Chen (JGI: Joint Genome Institute)H-Index: 22
#2Ken Chu (JGI: Joint Genome Institute)H-Index: 20
Last. Nikos C. Kyrpides (JGI: Joint Genome Institute)H-Index: 100
view all 17 authors...
Author(s): Chen, IMA; Chu, K; Palaniappan, K; Pillay, M; Ratner, A; Huang, J; Huntemann, M; Varghese, N; White, JR; Seshadri, R; Smirnova, T; Kirton, E; Jungbluth, SP; Woyke, T; Eloe-Fadrosh, EA; Ivanova, NN; Kyrpides, NC | Abstract: The Integrated Microbial Genomes a Microbiomes system v.5.0 (IMG/M: contains annotated datasets categorized into: archaea, bacteria, eukarya, plasmids, viruses, genome fragments, metagenomes, cell enrichments, single particle sorts, and m...
429 CitationsSource
#1Donovan H. Parks (UQ: University of Queensland)H-Index: 36
#2Maria Chuvochina (UQ: University of Queensland)H-Index: 14
Last. Philip Hugenholtz (UQ: University of Queensland)H-Index: 114
view all 7 authors...
Interpretation of microbial genome data will be improved by a fully revised bacterial taxonomy.
1,125 CitationsSource
#1Patrick H. BradleyH-Index: 8
#2Stephen Nayfach (LBNL: Lawrence Berkeley National Laboratory)H-Index: 18
Last. Katherine S. Pollard (UCSF: University of California, San Francisco)H-Index: 77
view all 3 authors...
The mechanisms by which different microbes colonize the healthy human gut versus other body sites, the gut in disease states, or other environments remain largely unknown. Identifying microbial genes influencing fitness in the gut could lead to new ways to engineer probiotics or disrupt pathogenesis. We approach this problem by measuring the statistical association between a species having a gene and the probability that the species is present in the gut microbiome. The challenge is that closely...
15 CitationsSource
#1Robert M. Bowers (JGI: Joint Genome Institute)H-Index: 23
#2Nikos C. Kyrpides (JGI: Joint Genome Institute)H-Index: 100
Last. Tanja Woyke (MPG: Max Planck Society)H-Index: 13
view all 54 authors...
We present two standards developed by the Genomic Standards Consortium (GSC) for reporting bacterial and archaeal genome sequences. Both are extensions of the Minimum Information about Any (x) Sequ ...
582 CitationsSource
#1Christian M. K. Sieber (University of California, Berkeley)H-Index: 20
#2Alexander J. Probst (University of California, Berkeley)H-Index: 32
Last. Jillian F. Banfield (University of California, Berkeley)H-Index: 136
view all 7 authors...
Microbial communities are critical to ecosystem function. A key objective of metagenomic studies is to analyse organism-specific metabolic pathways and reconstruct community interaction networks. This requires accurate assignment of assembled genome fragments to genomes. Existing binning methods often fail to reconstruct a reasonable number of genomes and report many bins of low quality and completeness. Furthermore, the performance of existing algorithms varies between samples and biotopes. Her...
283 CitationsSource
#1Robert D. Stewart (Edin.: University of Edinburgh)H-Index: 7
#2Marc D. Auffret (Scotland's Rural College)H-Index: 12
Last. Mick Watson (Edin.: University of Edinburgh)H-Index: 31
view all 12 authors...
The cow rumen is adapted for the breakdown of plant material into energy and nutrients, a task largely performed by enzymes encoded by the rumen microbiome. Here we present 913 draft bacterial and archaeal genomes assembled from over 800 Gb of rumen metagenomic sequence data derived from 43 Scottish cattle, using both metagenomic binning and Hi-C-based proximity-guided assembly. Most of these genomes represent previously unsequenced strains and species. The draft genomes contain over 69,000 prot...
221 CitationsSource
Cited By221
#1Yu-Hsiang Chen (NTU: National Taiwan University)
#2Pei-Wen Chiang (AS: Academia Sinica)H-Index: 12
Last. Sen-Lin Tang (AS: Academia Sinica)H-Index: 28
view all 0 authors...
Most of Earth’s bacteria have yet to be cultivated. The metabolic and functional potentials of these uncultivated microorganisms thus remain mysterious, and the metagenome-assembled genome (MAG) approach is the most robust method for uncovering these potentials. However, MAGs discovered by conventional metagenomic assembly and binning are usually highly fragmented genomes with heterogeneous sequence contamination. In this study, we combined Illumina and Nanopore data to develop a new workflow to...
#1Mindia A. S. Haryono (NUS: National University of Singapore)H-Index: 1
#2Yingyu Law (NTU: Nanyang Technological University)H-Index: 15
Last. Rohan B. H. Williams (NUS: National University of Singapore)H-Index: 16
view all 0 authors...
Analysis of metagenome data based on the recovery of draft genomes (so called metagenome-assembled genomes, or MAG) have assumed an increasingly central role in microbiome research in recent years. Microbial communities underpinning the operation of wastewater treatment plants are particularly challenging targets for MAG analysis due to their high ecological complexity, and remain important, albeit understudied, microbial communities that play a key role in mediating interactions between human a...
#1Yosuke Nishimura (UTokyo: University of Tokyo)H-Index: 10
#2Susumu Yoshizawa (UTokyo: University of Tokyo)H-Index: 17
Marine microorganisms are immensely diverse and play fundamental roles in global geochemical cycling. Recent metagenome-assembled genome studies, with special attention to large-scale projects such as Tara Oceans, have expanded the genomic repertoire of marine microorganisms. However, published marine metagenome data has not been fully explored yet. Here, we collected 2,057 marine metagenomes (>29 Tera bps of sequences) covering various marine environments and developed a new genome reconstructi...
#1Izaak Coleman (Columbia University)H-Index: 1
#2Tal Korem (Columbia University)H-Index: 16
A central paradigm in microbiome data analysis, which we term the genome-centric paradigm, is that a linear (non-branching) DNA sequence is the ideal representation of a microbial genome. This representation is natural, as microbes indeed have non-branching genomes. Tremendous discoveries in microbiology were made under this paradigm, but is it always optimal for microbiome research? In this Commentary, we claim that the realization of this paradigm in metagenomic assembly, a fundamental step in...
#1Shaojun Pan (Fudan University)H-Index: 1
#2Chengkai Zhu (Fudan University)
Last. Luis Pedro Coelho (Fudan University)H-Index: 28
view all 0 authors...
Metagenomic binning is the step in building metagenome-assembled genomes (MAGs) when sequences predicted to originate from the same genome are automatically grouped together. The most widely-used methods for binning are reference-independent, operating de novo and allow the recovery of genomes from previously unsampled clades. However, they do not leverage the knowledge in existing databases. Here, we propose SemiBin, an open source tool that uses neural networks to implement a semi-supervised a...
#1Julie Perreau (University of Texas at Austin)H-Index: 3
#2Nancy A. Moran (University of Texas at Austin)H-Index: 123
Animal hosts have initiated myriad symbiotic associations with microorganisms and often have maintained these symbioses for millions of years, spanning drastic changes in ecological conditions and lifestyles. The establishment and persistence of these relationships require genetic innovations on the parts of both symbionts and hosts. The nature of symbiont innovations depends on their genetic population structure, categorized here as open, closed or mixed. These categories reflect modes of inter...
#1Hilary P. Browne (Wellcome Trust Sanger Institute)H-Index: 17
#2Alexandre Almeida (Wellcome Trust Sanger Institute)H-Index: 15
Last. David Goulding (Wellcome Trust Sanger Institute)H-Index: 38
view all 11 authors...
Background null Human-to-human transmission of symbiotic, anaerobic bacteria is a fundamental evolutionary adaptation essential for membership of the human gut microbiota. However, despite its importance, the genomic and biological adaptations underpinning symbiont transmission remain poorly understood. The Firmicutes are a dominant phylum within the intestinal microbiota that are capable of producing resistant endospores that maintain viability within the environment and germinate within the in...
#1Kristopher Kieft (UW: University of Wisconsin-Madison)H-Index: 5
#2Adam M. Breister (UW: University of Wisconsin-Madison)H-Index: 2
Last. Srivatsan Raman (UW: University of Wisconsin-Madison)H-Index: 12
view all 12 authors...
Viruses influence the fate of nutrients and human health by killing microorganisms and altering metabolic processes. Organosulfur metabolism and biologically derived hydrogen sulfide play dynamic roles in manifestation of diseases, infrastructure degradation, and essential biological processes. Although microbial organosulfur metabolism is well studied, the role of viruses in organosulfur metabolism is unknown. Here, we report the discovery of 39 gene families involved in organosulfur metabolism...
1 CitationsSource
#1Sakura Onizuka (Kyushu University)H-Index: 1
#2Masaru Tanaka (Kyushu University)H-Index: 48
Last. Jiro Nakayama (Kyushu University)H-Index: 50
view all 4 authors...
Spores of certain species belonging to Firmicutes are efficiently germinated by nutrient germinators, such as amino acids, in addition to bile acid. We attempted to culture difficult-to-culture or yet-to-be cultured spore-forming intestinal bacteria, using a combination of bile acids and amino acids. The combination increased the number of colonies that formed on agar medium plated with ethanol-treated feces. The operational taxonomic units of these colonized bacteria were classified into two ty...
#1Jun-Jie Hou (Tianjin Medical University General Hospital)
#2Xin Wang (Tianjin Medical University General Hospital)H-Index: 1
Last. Bangmao Wang (Tianjin Medical University General Hospital)H-Index: 21
view all 6 authors...
Abstract Irritable bowel syndrome (IBS) is a common functional gastrointestinal disease that affects 3.8–9.2% of the world population. It affects the physiology and psychology of patients and increases the burden on families, the healthcare system, society, and economic development. Presently, a large number of studies have shown that compared to healthy individuals, the composition and diversity of gut microbiota in IBS patients have changed, and the proteolytic activity (PA) in fecal supernata...