The ecology of the microbiome: Networks, competition, and stability

Coyte, Katharine Z.; Schluter, Jonas; Foster, Kevin R.

doi:10.1126/science.aad2602

Cited by 1,705 publications

(1,511 citation statements)

References 53 publications

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“…A high-fiber diet might protect against the depletion of positive microbe-microbe interactions caused by the presence of oxygen. Negative interactions have been found to dominate stable microbial communities 44 . Based on our simulations, we propose that a small number of positive interactions may be sufficient to maintain a healthy microbial community.…”

Section: Pairwise Interactions Of Modelsmentioning

confidence: 99%

Generation of genome-scale metabolic reconstructions for 773 members of the human gut microbiota

et al. 2016

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1 r e s o u r c eChanges in the composition of the human gut microbiota have been associated with the development of chronic diseases including type 2 diabetes, obesity, and colorectal cancer 1 . Gut bacterial functions, such as synthesis of amino acids and vitamins 2 , breakdown of indigestible plant polysaccharides 3 , and production of metabolites involved in energy metabolism 4 , have been linked to human health. The use of 'omics approaches to study human microbiome communities has led to the generation of enormous data sets whose interpretations require systems biology tools to shed light on the functional capacity of gut microbiomes and their interactions with the human host 5 .In order to infer the metabolic repertoire of a gut metagenome data set, researchers usually map sequenced genes or organisms onto metabolic networks derived from the Kyoto Encyclopedia of Genes and Genomes (KEGG) 6 , and functional annotations from KEGG ontologies 7 . However, this approach cannot identify the contribution of each bacterial species to the metabolic repertoire of the whole gut microbiome, nor can it infer the effects of different gut microbial communities on host metabolism.A technique that can bridge this gap is constraint-based reconstruction and analysis (COBRA) 8 using genome-scale metabolic reconstructions (GENREs) of individual human gut microbes. GENREs are assembled using the genome sequence and experimental information 9 . These reconstructions form the basis for the development of condition-specific metabolic models whose functions are simulated and validated by comparison with experimental results. The models can be used to investigate genotype-phenotype relationships 10 , microbe-microbe interactions 11 , and host-microbe interactions 11 . Numerous tools can be used to automatically generate draft GENREs but such models contain errors 12 and are incomplete.Manual curation of draft reconstructions is time consuming because it involves an extensive literature review and experimental validation of metabolic functions 9 .To provide an extensive resource of GENREs for human gut microbes, we developed a comparative metabolic reconstruction method that enables any refinement to one metabolic reconstruction to be propagated to others. This accelerates reconstruction and improves model quality. We generated AGORA, which includes 773 gut microbes, comprising 205 genera and 605 species. All reconstructions were based on literature-derived experimental data and comparative genomics. The metabolic predictions of two AGORA reconstructions and their derived metabolic models were validated against experimental data. RESULTS Metabolic reconstruction pipelineWe devised a comparative metabolic reconstruction method (Fig. 1a,c), which is analogous to the comparative microbial genome annotation approach 13 that has enabled accelerated annotation by propagation of refinements to one genome to others. First, we downloaded draft GENREs using Model SEED 14 and KBase (US Department of Energy Systems Biology Knowledgebase, http:/...

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Section: Pairwise Interactions Of Modelsmentioning

confidence: 99%

Generation of genome-scale metabolic reconstructions for 773 members of the human gut microbiota

et al. 2016

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“…The gnotobiotic mouse model, combined with precise genetic manipulation of T6S activity in human symbionts, provides the opportunity to quantify effector transmission rates in the mammalian gut. To this end, we applied a special case of the generalized Lotka-Volterra model (5,18), which relates experimentally measured changes in the ratio of donor and recipient cells to the abundance of donor cells in the community and the effector transmission rate β:…”

Section: T6ss + B Fragilis Strains Target Susceptible Members Of Thementioning

confidence: 99%

“…Rates of in vivo T6SS activity were determined using a special case of the generalized Lotka-Volterra system commonly used to model microbiome dynamics (5,18). Details are available in SI Materials and Methods.…”

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confidence: 99%

Human symbionts inject and neutralize antibacterial toxins to persist in the gut

Wexler

Bao

Whitney

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

177

198

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The human gut microbiome is a dynamic and densely populated microbial community that can provide important benefits to its host. Cooperation and competition for nutrients among its constituents only partially explain community composition and interpersonal variation. Notably, certain human-associated Bacteroidetes—one of two major phyla in the gut—also encode machinery for contact-dependent interbacterial antagonism, but its impact within gut microbial communities remains unknown. Here we report that prominent human gut symbionts persist in the gut through continuous attack on their immediate neighbors. Our analysis of just one of the hundreds of species in these communities reveals 12 candidate antibacterial effector loci that can exist in 32 combinations. Through the use of secretome studies, in vitro bacterial interaction assays and multiple mouse models, we uncover strain-specific effector/immunity repertoires that can predict interbacterial interactions in vitro and in vivo, and find that some of these strains avoid contact-dependent killing by accumulating immunity genes to effectors that they do not encode. Effector transmission rates in live animals can exceed 1 billion events per minute per gram of colonic contents, and multiphylum communities of human gut commensals can partially protect sensitive strains from these attacks. Together, these results suggest that gut microbes can determine their interactions through direct contact. An understanding of the strategies human gut symbionts have evolved to target other members of this community may provide new approaches for microbiome manipulation.

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“…In addition, the production of secreted factors, such as bacteriocins, that competitively interfere or antagonize other strains/species, also contributes to a member's fitness in a community. In the microbe-dense human gut ecosystem, such factors and mechanisms of antagonism by predominant members are just beginning to be described, as are models predicting the relevance of these competitive interactions to the microbial community (1). Bacteroidales is the most abundant order of bacteria in the human colonic microbiota, and also the most temporally stable (2).…”

mentioning

confidence: 99%

Bacteroides fragilis type VI secretion systems use novel effector and immunity proteins to antagonize human gut Bacteroidales species

Chatzidaki‐Livanis

Geva‐Zatorsky

Comstock

2016

Proc. Natl. Acad. Sci. U.S.A.

171

166

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Type VI secretion systems (T6SSs) are multiprotein complexes best studied in Gram-negative pathogens where they have been shown to inhibit or kill prokaryotic or eukaryotic cells and are often important for virulence. We recently showed that T6SS loci are also widespread in symbiotic human gut bacteria of the order Bacteroidales, and that these T6SS loci segregate into three distinct genetic architectures (GA). GA1 and GA2 loci are present on conserved integrative conjugative elements (ICE) and are transferred and shared among diverse human gut Bacteroidales species. GA3 loci are not contained on conserved ICE and are confined to Bacteroides fragilis. Unlike GA1 and GA2 T6SS loci, most GA3 loci do not encode identifiable effector and immunity proteins. Here, we studied GA3 T6SSs and show that they antagonize most human gut Bacteroidales strains analyzed, except for B. fragilis strains with the same T6SS locus. A combination of mutation analyses, trans-protection analyses, and in vitro competition assays, allowed us to identify novel effector and immunity proteins of GA3 loci. These proteins are not orthologous to known proteins, do not contain identified motifs, and most have numerous predicted transmembrane domains. Because the genes encoding effector and immunity proteins are contained in two variable regions of GA3 loci, GA3 T6SSs of the species B. fragilis are likely the source of numerous novel effector and immunity proteins. Importantly, we show that the GA3 T6SS of strain 638R is functional in the mammalian gut and provides a competitive advantage to this organism.Bacteroides | T6SS | gut microbiota | bacterial competition | type VI secretion

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The ecology of the microbiome: Networks, competition, and stability

Cited by 1,705 publications

References 53 publications

Generation of genome-scale metabolic reconstructions for 773 members of the human gut microbiota

Generation of genome-scale metabolic reconstructions for 773 members of the human gut microbiota

Human symbionts inject and neutralize antibacterial toxins to persist in the gut

Bacteroides fragilis type VI secretion systems use novel effector and immunity proteins to antagonize human gut Bacteroidales species

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