BioModelsapplication/xmlhttps://www.ebi.ac.uk/biomodels/model/download/MODEL2002040003?filename=AP.xmlprimaryOK200Nana AnkrahNon-curatedconstraint-based modelL3V1https://www.ebi.ac.uk/biomodels/MODEL200204000333947801falseBioModelsSBMLModelsAnkrah2021 Genome scale metabolic model of Drosophila gut microbe Acetobacter pomorum2021MODEL2002040003Nana Ankrah, Barker B, Song J, Wu C, McMullen JG 2nd, Douglas AENana Ankrah33947801,
An important goal for many nutrition-based microbiome studies is to identify the metabolic function of microbes in complex microbial communities and their impact on host physiology. This research can be confounded by poorly understood effects of community composition and host diet on the metabolic traits of individual taxa. Here, we investigated these multiway interactions by constructing and analyzing metabolic models comprising every combination of five bacterial members of the <i>Drosophila</i> gut microbiome (from single taxa to the five-member community of <i>Acetobacter</i> and <i>Lactobacillus</i> species) under three nutrient regimes. We show that the metabolic function of <i>Drosophila</i> gut bacteria is dynamic, influenced by community composition, and responsive to dietary modulation. Furthermore, we show that ecological interactions such as competition and mutualism identified from the growth patterns of gut bacteria are underlain by a diversity of metabolic interactions, and show that the bacteria tend to compete for amino acids and B vitamins more frequently than for carbon sources. Our results reveal that, in addition to fermentation products such as acetate, intermediates of the tricarboxylic acid (TCA) cycle, including 2-oxoglutarate and succinate, are produced at high flux and cross-fed between bacterial taxa, suggesting important roles for TCA cycle intermediates in modulating <i>Drosophila</i> gut microbe interactions and the potential to influence host traits. These metabolic models provide specific predictions of the patterns of ecological and metabolic interactions among gut bacteria under different nutrient regimes, with potentially important consequences for overall community metabolic function and nutritional interactions with the host.<b>IMPORTANCE</b> <i>Drosophila</i> is an important model for microbiome research partly because of the low complexity of its mostly culturable gut microbiota. Our current understanding of how <i>Drosophila</i> interacts with its gut microbes and how these interactions influence host traits derives almost entirely from empirical studies that focus on individual microbial taxa or classes of metabolites. These studies have failed to capture fully the complexity of metabolic interactions that occur between host and microbe. To overcome this limitation, we reconstructed and analyzed 31 metabolic models for every combination of the five principal bacterial taxa in the gut microbiome of <i>Drosophila</i> This revealed that metabolic interactions between <i>Drosophila</i> gut bacterial taxa are highly dynamic and influenced by cooccurring bacteria and nutrient availability. Our results generate testable hypotheses about among-microbe ecological interactions in the <i>Drosophila</i> gut and the diversity of metabolites available to influence host traits.. 3, 6.
Department of Entomology, Cornell University, Ithaca, New York, USA nankr001@plattsburgh.edu.nankr001@plattsburgh.eduState University of New York at PlattsburghAn important goal for many nutrition-based microbiome studies is to identify the metabolic function of microbes in complex microbial communities and their impact on host physiology. This research can be confounded by poorly understood effects of community composition and host diet on the metabolic traits of individual taxa. Here, we investigated these multiway interactions by constructing and analyzing metabolic models comprising every combination of five bacterial members of the <i>Drosophila</i> gut microbiome (from single taxa to the five-member community of <i>Acetobacter</i> and <i>Lactobacillus</i> species) under three nutrient regimes. We show that the metabolic function of <i>Drosophila</i> gut bacteria is dynamic, influenced by community composition, and responsive to dietary modulation. Furthermore, we show that ecological interactions such as competition and mutualism identified from the growth patterns of gut bacteria are underlain by a diversity of metabolic interactions, and show that the bacteria tend to compete for amino acids and B vitamins more frequently than for carbon sources. Our results reveal that, in addition to fermentation products such as acetate, intermediates of the tricarboxylic acid (TCA) cycle, including 2-oxoglutarate and succinate, are produced at high flux and cross-fed between bacterial taxa, suggesting important roles for TCA cycle intermediates in modulating <i>Drosophila</i> gut microbe interactions and the potential to influence host traits. These metabolic models provide specific predictions of the patterns of ecological and metabolic interactions among gut bacteria under different nutrient regimes, with potentially important consequences for overall community metabolic function and nutritional interactions with the host.<b>IMPORTANCE</b> <i>Drosophila</i> is an important model for microbiome research partly because of the low complexity of its mostly culturable gut microbiota. Our current understanding of how <i>Drosophila</i> interacts with its gut microbes and how these interactions influence host traits derives almost entirely from empirical studies that focus on individual microbial taxa or classes of metabolites. These studies have failed to capture fully the complexity of metabolic interactions that occur between host and microbe. To overcome this limitation, we reconstructed and analyzed 31 metabolic models for every combination of the five principal bacterial taxa in the gut microbiome of <i>Drosophila</i> This revealed that metabolic interactions between <i>Drosophila</i> gut bacterial taxa are highly dynamic and influenced by cooccurring bacteria and nutrient availability. Our results generate testable hypotheses about among-microbe ecological interactions in the <i>Drosophila</i> gut and the diversity of metabolites available to influence host traits.Predicted Metabolic Function of the Gut Microbiota of Drosophila melanogaster.Ankrah Nana Y D NYD, Barker Brandon E BE, Song Joan J, Wu Cindy C, McMullen John G JG, Douglas Angela E AEsubgenus>, Drosophila <basidiomycete fungi>, digestive canal, scale tissue, fruit fly, AI747421, Drosophila Fallen, gut, scale, Genomes, lower gastrointestinal tract, plant peltate hair, Drosophilas, peltate hair, Fly, fruit fly <Drosophila>, Gus-u, alimentary tract, Gus-t, Gus-s, enteric tract, Gus-r, genus>, Fruit Flies, Drosophila Fruit, gut tube, Gus, Gur, Drosophila, Gut, g, gastrointestinal system, lower GI tract, Drosophila Fruit Fly, scale (sensu Metazoa), digestive tube, Fruit Fly, asd, fruit flies, scales, alimentary system, Flies, Drosophila <flies, 1823, Drosophila Fruit Flies, alimentary canal.subgenus>, host organism, fruit fly, cox4, Activity, Laboratory, Termobacterium, postnatal development, Aminosaeure, fond, ethanoate, Amino acid, growth and development, sci, CycEI, composed of, fish eye disease, Readability, primary metabolites, Ccne, Carbon-12, HOW, How, AW048865, Research Activity, DmelCG10664, Laboratory Research, Flies, l(3)j5D5, Priorities, 24B, C, me75, Eubacteria, alpha-ketoglutarate, amino acids, availability, COXIV, Drosophilas, Microbial Community Structure, Fly, alimentary tract, stru, composition, l(3)S053606, COXA_DROME, CG10293, "Acetobacterium" Ludwig 1898, D17Mit170, T1, CH3-COO(-), l(3)j5B5, g, Bacteria <bacteria>, Prokaryotae, Carbon, Microbial Community Structures, fish-eye disease, digestive tube, asd, Procaryotae, Research Priority, fruit flies, alimentary system, 0904/17, lower gastrointestinal tract, Aminokarbonsaeure, Krebs cycle, ACETATE ION, 2-oxopentanedioic acid, Research Priorities, Cyc E, br37, Tl3, Microbial, Fermentations, Tl2, alpha-amino carboxylic acids, results, alpha-lecithin cholesterol acyltransferase deficiency, Vitreous, BG:DS07108.3, SZ1, prokaryotes, COX IV, l(2)05206, Ethanoat, Microbial Communities, 1823, Research and Development, Amino Acid, Acid, Drosophila <basidiomycete fungi>, AI747421, Amino acids, growth pattern, Microbial Community Compositions, Va, non-developmental growth, 6C, content, succinate, fruit fly <Drosophila>, Activities, Composition, Vitreous Carbon, Drosophila, l35Dd, gastrointestinal system, Festa, Drosophila Fruit Fly, metabolites, carbonium, anon-EST:Liang-2.39, Acids, DmelCG14724, E430016J11Rik, Human Microbiomes, Prokaryota, Community, Drosophila <flies, Drosophila Fruit Flies, digestive canal, Microbial Community Composition, LCATA deficiency, Drosophila Fallen, cycline, Mycoderma, FESTA-L, FESTA-S, P62, DmcyclinE, Aminocarbonsaeure, Goal, secondary metabolites, enteric tract, Traits., carbon, cycE, eubacteria, alpha-amino acid, Ximpact, l(2)br37, CYCLE, Human, cdi7, CG10664, alpha-lecithin:cholesterol acyltransferase deficiency, Gus, Gur, Gut, cyclinE, Azetat, IV, Diets, Cdi7, CDI7, citric acid cycle, Low, U19, Partial LCAT deficiency, dyslipoproteinemic corneal dystrophy, BM040, gut, CYCE, FOCUS, l(3)s2612, Research, DmelCG3938, CyclE, nutrients, acetate, partial LCAT deficiency, 3938, DmcycE, Monera, Drosophila Fruit, Paralactobacillus, Commensalism, l(2)k05007, Kohlenstoff, dm-cycE, FED, lower GI tract, COX, 2-oxopentanedioate, DmelCG10293, Development and Research, species, fungi, 2-oxoglutarate, Human Microbiome, mutualism, Acetimonas, nutrient, bacteria, 2-ketoglutarate, fed, Community Composition, cou, clone 2.39, Traits, ion(1-), genus>, function, alpha-amino acids, compositionality, qkr, carbone, l(3)S090417, impact-a, carbono, development, gut tube, Priority, Lr, l(2)k02514, DmCycE, KH93F, Research Activities, butanedioic acid, CyeE, alimentary canal, Microbiome, who, l(2)k02602, Microbiomes, butanedioate, alpha-LCAT deficiency, Microbial Community, Mutualism, Dietary, postnatal growth, tend, l(2)35Dd, Gus-u, Community Structure, Gus-t, metabolite, Gus-s, Gus-r, ion(2-), Who/How, Understanding, Amino, TRAITS, Fruit Flies, Carbon 12, D-CycE, CG14724, TCA cycle, Ulvina, prokaryote, structure, MeCO2 anion, Bra, qkr[93F], Microbiotas, Fruit Fly, B Vitamins, Endosymbiosis, (-)OOC-CH2-CH2-COO(-), responsive, acetic acid, growth, CG3938, RWDD5subgenus>, host organism, fruit fly, Activity, Laboratory, Termobacterium, postnatal development, Aminosaeure, fond, ethanoate, Amino acid, growth and development, CycEI, composed of, fish eye disease, Ccne, Carbon-12, AW048865, Research Activity, Laboratory Research, Flies, Priorities, C, Eubacteria, alpha-ketoglutarate, amino acids, Drosophilas, Fly, alimentary tract, composition, "Acetobacterium" Ludwig 1898, CH3-COO(-), g, Bacteria <bacteria>, Prokaryotae, Carbon, fish-eye disease, digestive tube, asd, Procaryotae, Research Priority, fruit flies, alimentary system, lower gastrointestinal tract, Aminokarbonsaeure, Krebs cycle, ACETATE ION, 2-oxopentanedioic acid, Research Priorities, Cyc E, br37, Fermentations, alpha-amino carboxylic acids, results, alpha-lecithin cholesterol acyltransferase deficiency, Vitreous, BG:DS07108.3, prokaryotes, l(2)05206, Ethanoat, 1823, Research and Development, Amino Acid, Acid, Drosophila <basidiomycete fungi>, AI747421, Amino acids, growth pattern, non-developmental growth, 6C, content, succinate, fruit fly <Drosophila>, Activities, Vitreous Carbon, Drosophila, l35Dd, gastrointestinal system, Festa, Drosophila Fruit Fly, carbonium, Acids, E430016J11Rik, Prokaryota, Drosophila <flies, Drosophila Fruit Flies, digestive canal, LCATA deficiency, Drosophila Fallen, cycline, Mycoderma, FESTA-L, FESTA-S, DmcyclinE, Aminocarbonsaeure, Goal, enteric tract, carbon, cycE, eubacteria, alpha-amino acid, Ximpact, l(2)br37, CYCLE, cdi7, alpha-lecithin:cholesterol acyltransferase deficiency, Gus, Gur, Gut, cyclinE, Azetat, Diets, Cdi7, CDI7, citric acid cycle, U19, Partial LCAT deficiency, dyslipoproteinemic corneal dystrophy, BM040, gut, CYCE, Research, DmelCG3938, CyclE, nutrients, acetate, partial LCAT deficiency, 3938, DmcycE, Monera, Drosophila Fruit, Paralactobacillus, Commensalism, l(2)k05007, Kohlenstoff, dm-cycE, FED, lower GI tract, 2-oxopentanedioate, Development and Research, species, fungi, 2-oxoglutarate, mutualism, Acetimonas, nutrient, bacteria, 2-ketoglutarate, fed, Traits, ion(1-), genus>, function, alpha-amino acids, compositionality, carbone, impact-a, carbono, development, gut tube, Priority, l(2)k02514, DmCycE, Research Activities, butanedioic acid, CyeE, alimentary canal, l(2)k02602, butanedioate, alpha-LCAT deficiency, Mutualism, Dietary, postnatal growth, l(2)35Dd, Gus-u, Gus-t, Gus-s, Gus-r, ion(2-), Amino, TRAITS, Fruit Flies, Carbon 12, D-CycE, TCA cycle, Ulvina, prokaryote, structure, MeCO2 anion, Fruit Fly, B Vitamins, Endosymbiosis, (-)OOC-CH2-CH2-COO(-), responsive, acetic acid, growth, CG3938, host organism., RWDD5digestive canal, Microbial Community Composition, AI747421, Community Composition, fruit fly, gut, Microbiomes, Microbial Community Compositions, lower gastrointestinal tract, Microbial Community, Microbial Community Structure, Gus-u, alimentary tract, Community Structure, Gus-t, Gus-s, enteric tract, Gus-r, Drosophila melanogasters., Sophophora melanogaster, Microbial, melanogaster, D. melanogaster, predicted, Human, Composition, gut tube, Gus, Gur, Drosophila, Gut, g, gastrointestinal system, lower GI tract, Drosophila melangaster, Microbial Community Structures, digestive tube, Microbiotas, asd, alimentary system, alimentary canal, Human Microbiomes, Microbial Communities, Community, Human Microbiome, MicrobiomefalseAnkrah2021 - Genome scale metabolic model of Drosophila gut microbe Acetobacter pomorumAn important goal for many nutrition-based microbiome studies is to identify the metabolic function of microbes in complex microbial communities and its impact on host physiology. This research can be confounded by poorly-understood effects of community composition and host diet on the metabolic traits of individual taxa. Here, we investigated these multi-way interactions by constructing and analyzing metabolic models comprising every combination of five bacterial members of the Drosophila gut microbiome (from single taxa to the five-member community of Acetobacter and Lactobacillus species) under three nutrient regimes. We show that the metabolic function of Drosophila gut bacteria is dynamic, influenced by community composition and responsive to dietary modulation. Furthermore, we show that ecological interactions such as competition and mutualism identified from the growth patterns of gut bacteria are underlain by a diversity of metabolic interactions, and show that the bacteria tend to compete for amino acids and B vitamins more frequently than for carbon sources. Our results reveal that in addition to fermentation products such as acetate, intermediates of the tricarboxylic acid (TCA) cycle including 2-oxoglutarate and succinate are produced at high flux and cross-fed between bacterial taxa suggesting important roles for TCA cycle intermediates in modulating Drosophila gut microbe interactions and the potential to influence host traits. These metabolic models provide specific predictions of the patterns of ecological and metabolic interactions among gut bacteria under different nutrient regimes, with potentially important consequences for overall community metabolic function and nutritional interactions with the 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