An integrated catalog of reference genes in the human gut microbiome

Li, Junhua; Jia, Huijue; Cai, Xianghang; Huang, Zhong; Feng, Qiang; Sunagawa, Shinichi; Arumugam, Manimozhiyan; Kultima, Jens Roat; Prifti, Edi; Nielsen, Trine; Juncker, Agnieszka Sierakowska; Manichanh, Chaysavanh; Chen, Bing; Zhang, Wenwei; Levenez, Florence; Wang, Juan; Xu, Xun; Xiao, Liang; Liang, Suisha; Zhang, Dongya; Zhang, Zhaoxi; Chen, Wei-Neng; Zhao, Hailong; Al‐Aama, Jumana Y.; Edris, Sherif; Yang, Huanming; Wang, Jian; Hansen, Torben; Nielsen, Henrik Bjørn; Brunak, Søren; Kristiansen, Karsten; Guarner, Francisco; Pedersen, Oluf; Doré, Joël; Ehrlich, S. Dusko; Bork, Peer; Wang, Jun

doi:10.1038/nbt.2942

Cited by 1,619 publications

(1,480 citation statements)

References 51 publications

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“…Metagenomic reads were mapped against the integrated gene catalogue (IGC) 60 and genus-level abundance profiles were calculated as described in the publication of the integrated gene catalogue 60 . These profiles were concatenated with the profiles of 1,267 samples distributed with the IGC.…”

Section: Methodsmentioning

confidence: 99%

Integrated multi-omics of the human gut microbiome in a case study of familial type 1 diabetes

et al. 2016

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The gastrointestinal microbiome is a complex ecosystem with functions that shape human health. Studying the relationship between taxonomic alterations and functional repercussions linked to disease remains challenging. Here, we present an integrative approach to resolve the taxonomic and functional attributes of gastrointestinal microbiota at the metagenomic, metatranscriptomic and metaproteomic levels. We apply our methods to samples from four families with multiple cases of type 1 diabetes mellitus (T1DM). Analysis of intra-and inter-individual variation demonstrates that family membership has a pronounced effect on the structural and functional composition of the gastrointestinal microbiome. In the context of T1DM, consistent taxonomic differences were absent across families, but certain human exocrine pancreatic proteins were found at lower levels. The associated microbial functional signatures were linked to metabolic traits in distinct taxa. The methodologies and results provide a foundation for future large-scale integrated multi-omic analyses of the gastrointestinal microbiome in the context of host-microbe interactions in human health and disease.

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Section: Methodsmentioning

confidence: 99%

Integrated multi-omics of the human gut microbiome in a case study of familial type 1 diabetes

et al. 2016

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“…To generate such gene profiles, we mapped all metagenomic reads to the integrated gene catalog (IGC) from Li et al (2014). Additionally, species abundance was correlated with the IGC.…”

Section: Methodsmentioning

confidence: 99%

Subspecies in the global human gut microbiome

Costea

Coelho

Sunagawa

et al. 2017

Molecular Systems Biology

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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.

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“…Obviously, this approach cannot take into account all the complexity of the intestinal milieu and it could miss some regulations due to pH, pO 2 , microbial cooperation and trans-kingdom interactions. Improvements of translational models, as the recent organ-on-chip development, will provide additional tools to partially overcome challenges that relate to host complexity and host cell differentiation issues of relevance for in vitro culture systems [89].…”

Section: Microbiota As Source Of Novel Drugs Adjuvants and Targetsmentioning

confidence: 99%

“…Its structure at the genome level is known as the microbiome -a term introduced by the Nobel laureate Joshua Lederberg to describe the collective genomic content of the gut microbiota. The diversity of the microbiome is huge, with around 10 million non-redundant genes described to date [2], compared to the 24 000 human genes. The 2 kg of microbial biomass in the gut gathers 100 trillion of bacteria which represents in numbers more than there are human cells.…”

Section: Introductionmentioning

confidence: 99%

The human gut microbiome as source of innovation for health: Which physiological and therapeutic outcomes could we expect?

2017

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Summary From the moment of birth, each human being builds a microbe-host symbiosis which is key for the preservation of its health and well-being. This personal symbiotic coexistence is the result of progressive enrichments in microorganism diversity through external supplies. This diversity is nowadays massively overthrown by drastic changes related to clinical practice in birth management, environmental exposure, nutrition and healthcare behaviors. The last two generations have been the frame of massive modifications in life and food habits, with people being more and more sedentary, overfed and permeated with drugs and pollutants. We are now able to measure the impact of these changes on the gut microbiota diversity. Concomitantly, these modifications of lifestyle were associated with a dramatic increase in incidence of immune-mediated diseases including metabolic, allergic and inflammatory diseases and most likely neurodegenerative and psychiatric disorders. Microbiota is becoming a hot topic in the scientific community and in the mainstream media. The number of scientific publications increased by up to a factor three over the last five years, with gastrointestinal and metabolic diseases being the most productive areas. In the intellectual property landscape, the patent families on microbiota have more than doubled in the meantime. In parallel, funding either from National Institutes (e.g. from NIH which funds research mainly in the field of allergies, infections, cancer and cardiovascular diseases, from the White House which launched the national microbiome initiative) or by pharmaceutical companies follow the same trend, showing a boost and a strong support in the research field on microbiota. All major health players are investing in microbiome research as shown by the number of deals signed and by funding during 2015. The Giens round table addressed how the medicine of tomorrow, considering human beings as a human-microbe symbiotic supraorganism, could leverage microbiome knowledge and tools. The rationale for our working group has been structured around four domains of innovation that could derive from ongoing efforts in deciphering the interactions between human cells and intestinal microbiome as a central component of human health, namely: (1) development of stratification and monitoring tools; (2) identification of new target and drug discovery, as a part of our supra-genome; (4) exploitation of microbiota as a therapeutic target that can be modulated; (4) and finally as a source of live biotherapeutics and adjuvants. These four streams will exemplify how microbiota has changed the way we consider a wide range of chronic and incurable diseases and the consequences of long-lasting dysbiosis. In-depth microbiota analysis is opening one of the broadest fields of investigation for improving human and animal health and will be a source of major therapeutic innovations for tackling today's medical unmet needs. We thus propose a range of recommendations for basic researchers, care givers as well as for hea...

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An integrated catalog of reference genes in the human gut microbiome

Cited by 1,619 publications

References 51 publications

Integrated multi-omics of the human gut microbiome in a case study of familial type 1 diabetes

Integrated multi-omics of the human gut microbiome in a case study of familial type 1 diabetes

Subspecies in the global human gut microbiome

The human gut microbiome as source of innovation for health: Which physiological and therapeutic outcomes could we expect?

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