A library of human gut bacterial isolates paired with longitudinal multiomics data enables mechanistic microbiome research

Poyet, Mathilde; Gibbons, Sean M.; Ávila-Pacheco, Julián; Jiang, Xiaofang; Kearney, Sean M.; Perrotta, Alessandra; Berdy, Brittany; Zhao, Shijie; Lieberman, Tami D.; Swanson, Patricia; Smith, Mark; Roesemann, Shane D; Alexander, Jacob; Rich, Suzanna; Livny, Jonathan; Vlamakis, Hera; Clish, Clary B.; Bullock, Kevin; Deik, Amy; Scott, Justine A; Pierce, Kerry A.; Xavier, Ramnik J.; Alm, Eric J.

doi:10.1038/s41591-019-0559-3

Cited by 299 publications

(408 citation statements)

References 71 publications

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“…Sequencing libraries targeting the V4 region of the 16S rRNA gene were prepared by the MOC core facility at the Broad Institute, Cambridge, MA, USA and sequenced as 150 bp paired-end reads in two runs on an Illumina MiSeq. 300 (as described in 53 ), resulting in an average of 61,617 ± 43,997 (st. dev.)…”

Section: Discussionmentioning

confidence: 99%

Response of the human gut and saliva microbiome to urbanization in Cameroon

Lokmer

Aflalo

Amougou

et al. 2020

Sci Rep

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Urban populations from highly industrialized countries are characterized by a lower gut bacterial diversity as well as by changes in composition compared to rural populations from less industrialized countries. to unveil the mechanisms and factors leading to this diversity loss, it is necessary to identify the factors associated with urbanization-induced shifts at a smaller geographical scale, especially in less industrialized countries. to do so, we investigated potential associations between a variety of dietary, medical, parasitological and socio-cultural factors and the gut and saliva microbiomes of 147 individuals from three populations along an urbanization gradient in cameroon. We found that the presence of Entamoeba sp., a commensal gut protozoan, followed by stool consistency, were major determinants of the gut microbiome diversity and composition. interestingly, urban individuals have retained most of their gut eukaryotic and bacterial diversity despite significant changes in diet compared to the rural areas, suggesting that the loss of bacterial microbiome diversity observed in industrialized areas is likely associated with medication. finally, we observed a weak positive correlation between the gut and the saliva microbiome diversity and composition, even though the saliva microbiome is mainly shaped by habitat-related factors.Humans living in urban areas from highly industrialized countries host less diverse gut microbiomes than those in rural areas from the less industrialized ones. This effect of industrialization (as we refer to it hereafter) has been reported by numerous studies comparing urban areas in Europe or North America with rural ones in Africa, Asia or South America 1-8 . Loss in alpha diversity is further accompanied by systematic shifts in bacterial composition (see e.g. 9,10 ). Despite crucial implications for human health 11,12 , the factors responsible for these ecological changes are still unclear. Two main (non-exclusive) hypotheses have been proposed: (i) decreased consumption of dietary fibers 13,14 and (ii) improved sanitation and access to medical care (including antibiotics 15 ). In addition, geographical latitude could be a confounding factor, given that it is a proxy for the diversity of environmental bacteria 16 . Indeed, the only two studies that did not find a loss of diversity with industrialization were studies considering rural populations not living in a warm tropical environment 17,18 .To disentangle various factors potentially leading to this observed diversity loss, some authors focused on smaller geographical scales, contrasting urban and rural individuals from the same countries (referred to hereafter as the effect of urbanization). Such studies reported inconsistent results: no significant differences in Russia 19 and Nigeria 20 , some differences in China 21 , and season and altitude dependent shifts in Mongolia 22 and India 23 , respectively. These discrepancies can be partially explained by different definitions of rural areas used in these studies (from iso...

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Section: Discussionmentioning

confidence: 99%

Response of the human gut and saliva microbiome to urbanization in Cameroon

Lokmer

Aflalo

Amougou

et al. 2020

Sci Rep

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“…Of the 4,644 species contained in the UHGG, 71% lack a cultured representative, meaning the majority of microbial diversity in the catalogue remains to be experimentally characterized. During preparation of our manuscript, a new collection of almost 4,000 cultured genomes from 106 gut species was released 38 , which will be incorporated in future versions of the resource. As 96% of these genomes were reported to have a species representative in the culture collections here included, we do not anticipate this dataset to provide a substantial increase in the number of species discovered.…”

Section: Discussionmentioning

confidence: 99%

A unified sequence catalogue of over 280,000 genomes obtained from the human gut microbiome

Almeida

Nayfach

Boland

et al. 2019

Preprint

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26Comprehensive reference data is essential for accurate taxonomic and functional 27 characterization of the human gut microbiome. Here we present the Unified Human 28Gastrointestinal Genome (UHGG) collection, a resource combining 286,997 genomes 29 representing 4,644 prokaryotic species from the human gut. These genomes contain over 625 30 million protein sequences used to generate the Unified Human Gastrointestinal Protein 31 (UHGP) catalogue, a collection that more than doubles the number of gut protein clusters over 32 the Integrated Gene Catalogue. We find that a large portion of the human gut microbiome 33 remains to be fully explored, with over 70% of the UHGG species lacking cultured 34 representatives, and 40% of the UHGP missing meaningful functional annotations. Intra-35 species genomic variation analyses revealed a large reservoir of accessory genes and single-36 nucleotide variants, many of which were specific to individual human populations. These freely 37 available genomic resources should greatly facilitate investigations into the human gut 38 microbiome. 39 3 Main 40 The human gut microbiome has been implicated in important phenotypes related to human 41 health and disease 1,2 . However, incomplete reference data that are missing microbial diversity 3 42 hamper our understanding of the roles of individual microbiome species, their interactions and 43 functions. Hence, establishing a comprehensive collection of microbial reference genomes and 44 genes is an important step for accurate characterization of the taxonomic and functional 45 repertoire of the intestinal microbial ecosystem. 46 47The Human Microbiome Project (HMP) 4 was a pioneering initiative to enrich our knowledge ( Supplementary Fig. 2), a standardized taxonomic framework based on a concatenated protein 112 phylogeny representing >140,000 public prokaryote genomes, fully resolved to the species 113 level (see 'Methods' for details on the taxonomy nomenclature used). However, over 60% of 114 6 the gut genomes could not be assigned to an existing species, confirming the majority of the 115 UHGG species lack representation in current reference databases. 116 117 Comparison of species recovered in individual studies 118We investigated how many of the 4,644 gut species were found in the different study 119 collections in order to determine their level of overlap and reproducibility, as well as the ratio 120 between cultured and uncultured species (Fig. 2a). The largest intersection was between the 121 collections of MAGs, with the same 1,081 species detected independently in the CIBIO, EBI 122 and HGM datasets, but not in any of the cultured genome studies. By restricting the analysis to 123 genomes recovered from 1,554 samples common to all three MAG studies, we found that 93-124 97% of species from each set were detected in at least one other MAG collection, and 79-86% 125 across all three ( Supplementary Fig. 3a). Similar level of species overlap was observed when 126 comparing studies on a per-sample basis ( Supplementary Fig. 3b). F...

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“…The Genome Tree Database improves taxonomic resolution of k-mer based approaches Historically, microbial sequencing efforts focused predominantly on a small number of organisms, often causes of nosocomial infections [ Figure S1A,B]. By contrast, reference databases, including NCBI Genbank, are increasingly populated with genomic information of commensal microbes (Browne et al, 2016;Forster et al, 2019;Poyet et al, 2019;Zou et al, 2019). As genome reference databases expand, historical, microbiological-based taxonomic assignments do not reflect population level relationships inferred from genome sequencing.…”

Section: Resultsmentioning

confidence: 99%

Stability and dynamics of the human gut microbiome and its association with systemic immune traits

Byrd¹,

Liu

Fujimura³

et al. 2020

Preprint

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Analysis of 1,363 deeply sequenced gut microbiome samples from 946 healthy donors of the Milieu Intérieur cohort provides new opportunities to discover how the gut microbiome is associated with host factors and lifestyle parameters. Using a genomebased taxonomy to achieve higher resolution analysis, we found an enrichment of Prevotella species in males, and that bacterial profiles are dynamic across five decades of life (20-69), with Bacteroidota species consistently increased with age while Actinobacteriota species, including Bifidobacterium, decreased. Longitudinal sampling revealed short-term stability exceeds inter-individual differences; however, the degree of stability was variable between donors and influenced by their baseline community composition. We then integrated the microbiome results with systemic immunophenotypes to show that host/microbe associations discovered in animal models, such as T regulatory cells and short chain fatty acids, could be validated in human data.These results will enable personalized medicine approaches for microbial therapeutics and biomarkers. ¶ unless otherwise indicated, partners are located at

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A library of human gut bacterial isolates paired with longitudinal multiomics data enables mechanistic microbiome research

Cited by 299 publications

References 71 publications

Response of the human gut and saliva microbiome to urbanization in Cameroon

Response of the human gut and saliva microbiome to urbanization in Cameroon

A unified sequence catalogue of over 280,000 genomes obtained from the human gut microbiome

Stability and dynamics of the human gut microbiome and its association with systemic immune traits

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