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1,520 reference genomes from cultivated human gut bacteria enable functional microbiome analyses.

ABSTRACT: 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 increase in the number of reference bacterial genomes improves the rate of mapping metagenomic sequencing reads from 50% to >70%, enabling higher-resolution descriptions of the human gut microbiome. We use the CGR genomes to annotate functions of 338 bacterial species, showing the utility of this resource for functional studies. We also carry out a pan-genome analysis of 38 important human gut species, which reveals the diversity and specificity of functional enrichment between their core and dispensable genomes.

SUBMITTER: Zou Y

PROVIDER: S-EPMC6784896 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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1,520 reference genomes from cultivated human gut bacteria enable functional microbiome analyses.

Zou Yuanqiang Y Xue Wenbin W Luo Guangwen G Deng Ziqing Z Qin Panpan P Guo Ruijin R Sun Haipeng H Xia Yan Y Liang Suisha S Dai Ying Y Wan Daiwei D Jiang Rongrong R Su Lili L Feng Qiang Q Jie Zhuye Z Guo Tongkun T Xia Zhongkui Z Liu Chuan C Yu Jinghong J Lin Yuxiang Y Tang Shanmei S Huo Guicheng G Xu Xun X Hou Yong Y Liu Xin X Wang Jian J Yang Huanming H Kristiansen Karsten K Li Junhua J Jia Huijue H Xiao Liang L

Nature biotechnology 20190204 2

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 ...[more]

PMID: 30718868

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Project description:BackgroundMetagenome sampling bias for geographical location and lifestyle is partially responsible for the incomplete catalog of reference genomes of gut microbial species. Thus, genome assembly from currently under-represented populations may effectively expand the reference gut microbiome and improve taxonomic and functional profiling.MethodsWe assembled genomes using public whole-metagenomic shotgun sequencing (WMS) data for 110 and 645 fecal samples from India and Japan, respectively. In addition, we assembled genomes from newly generated WMS data for 90 fecal samples collected from Korea. Expecting genome assembly for low-abundance species may require a much deeper sequencing than that usually employed, so we performed ultra-deep WMS (> 30 Gbp or > 100 million read pairs) for the fecal samples from Korea. We consequently assembled 29,082 prokaryotic genomes from 845 fecal metagenomes for the three under-represented Asian countries and combined them with the Unified Human Gastrointestinal Genome (UHGG) to generate an expanded catalog, the Human Reference Gut Microbiome (HRGM).ResultsHRGM contains 232,098 non-redundant genomes for 5414 representative prokaryotic species including 780 that are novel, > 103 million unique proteins, and > 274 million single-nucleotide variants. This is an over 10% increase from the UHGG. The new 780 species were enriched for the Bacteroidaceae family, including species associated with high-fiber and seaweed-rich diets. Single-nucleotide variant density was positively associated with the speciation rate of gut commensals. We found that ultra-deep sequencing facilitated the assembly of genomes for low-abundance taxa, and deep sequencing (e.g., > 20 million read pairs) may be needed for the profiling of low-abundance taxa. Importantly, the HRGM significantly improved the taxonomic and functional classification of sequencing reads from fecal samples. Finally, analysis of human self-antigen homologs on the HRGM species genomes suggested that bacterial taxa with high cross-reactivity potential may contribute more to the pathogenesis of gut microbiome-associated diseases than those with low cross-reactivity potential by promoting inflammatory condition.ConclusionsBy including gut metagenomes from previously under-represented Asian countries, Korea, India, and Japan, we developed a substantially expanded microbiome catalog, HRGM. Information of the microbial genomes and coding genes is publicly available ( www.mbiomenet.org/HRGM/ ). HRGM will facilitate the identification and functional analysis of disease-associated gut microbiota.

Project description:Since cheese is one of the most commonly and globally consumed fermented foods, scientific investigations in recent decades have focused on determining the impact of this dairy product on human health and well-being. However, the modulatory effect exerted by the autochthonous cheese microbial community on the taxonomic composition and associated functional potential of the gut microbiota of human is still far from being fully dissected or understood. Here, through the use of an in vitro human gut-simulating cultivation model in combination with multi-omics approaches, we have shown that minor rather than dominant bacterial players of the cheese microbiota are responsible for gut microbiota modulation of cheese consumers. These include taxa from the genera Enterococcus, Bacillus, Clostridium, and Hafnia. Indeed, they contribute to expand the functional potential of the intestinal microbial ecosystem by introducing genes responsible for the production of metabolites with relevant biological activity, including genes involved in the synthesis of vitamins, short-chain fatty acids, and amino acids. Furthermore, tracing of cheese microbiota-associated bacterial strains in fecal samples from cheese consumers provided evidence of horizontal transmission events, enabling the detection of particular bacterial strains transferred from cheese to humans. Moreover, transcriptomic and metabolomic analyses of a horizontally transmitted (cheese-to-consumer) bacterial strain, i.e., Hafnia paralvei T10, cultivated in a human gut environment-simulating medium, confirmed the concept that cheese-derived bacteria may expand the functional arsenal of the consumer's gut microbiota. This highlights the functional and biologically relevant contributions of food microbes acquired through cheese consumption on the human health.IMPORTANCEDiet is universally recognized as the primary factor influencing and modulating the human intestinal microbiota both taxonomically and functionally. In this context, cheese, being a fermented food with its own microbiota, serves not only as a source of nourishment for humans, but also as a source of nutrients for the consumer's gut microbiota. Additionally, it may act as a vehicle for autochthonous food-associated microorganisms which undergo transfer from cheese to the consumer, potentially influencing host gut health. The current study highlights not only that cheese microbiota-associated bacteria can be traced in the human gut microbiota, but also that they may expand the functional repertoire of the human gut microbiota, with potentially significant implications for human health.

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1,520 reference genomes from cultivated human gut bacteria enable functional microbiome analyses.

Publications

1,520 reference genomes from cultivated human gut bacteria enable functional microbiome analyses.

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