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EliasNot availableEpithelial CellFecesFecal proteomics was conducted as previously described (Lichtman et al., 2013) with the following notable changes. Instead of analyzing all 4 fractions (20%, 40%, 60% and 100% acetonitrile) from the C4 solid-phase extraction chromatography, only the 40% and 60% fractions were digested and analyzed. Each sample was only analyzed with no technical replicates on a LTQ-Orbitrap Velos mass spectrometer (Thermo Scientific, San Jose).PrideJoshua E EliasLTQ Orbitrap VelosDepartment of Chemical & Systems Biology, Stanford UniversityPARTIAL26832403 Lichtman JS, Ferreyra JA, Ng KM, Smits SA, Sonnenburg JL, Elias JE. Host-Microbiota Interactions in the Pathogenesis of Antibiotic-Associated Diseases. Cell Rep. 2016 Jan 27. pii: S2211-1247(16)00029-2 10.1016/j.celrep.2016.01.009Chan Zuckerberg Biohubjosh.elias@stanford.eduMass SpectrometryShotgun proteomicsOpportunistic Bacterial Infectious DiseaseAntibioticMouseGutInflammationPathogenMicrobiomehttp://www.ebi.ac.uk/pride/archive/projects/PXD003152Spectrum countingmonohydroxylated residuethe msConvert program (v3.0.45) was used to generate peak lists from the original data and spectra were assigned to peptides using the SEQUEST (v28.12) (Eng et al., 1994) algorithm. Spectra were queried against a composite “target-decoy” sequence database consisting of the mouse proteome (Uniprot, downloaded October 30, 2012) and reversed decoy versions of the same sequences(Elias and Gygi, 2007). SEQUEST search parameters included using a semi-specific enzyme specificity, 50 ppm precursor mass tolerance, 1 Da fragment ion mass tolerance, static carbidomethylation of cysteines and differential methionine oxidation and glutamine/asparagine deamidation. Each mass spectrometry run was filtered to a 1% peptide FDR and the experiment-wide FDR was filtered to 5% using a linear discriminant analysis(Huttlin et al., 2010). All raw data is available on the PRIDE repository (Vizcaíno et al., 2013) with the dataset identifier [PDX__].” Spectral counts were normalized as a percentage of the total counts for a given fecal sample. Fold changes and statistical tests were performed using the QSpec software package (Choi et al., 2008). Centroid clustering was conducted on normalized spectral counts after normalizing to the abundance of each protein using Cluster (v 3.0) and visualized using Treeview (v 1.1.6r4). Principal component analysis was conducted on normalized spectral counts using the princomp function in Matlab (v 2012a). Proteins were identified as part of particular pathways using Ingenuity Pathway Analysis and gene ontology enrichments were calculated with DAVID (Huang et al., 2009a, 2009b)ProteomicsMus Musculus (mouse)josh.elias@stanford.eduBiomedicalUnited StatesImproved understanding of the interplay between host and microbes stands to illuminate new avenues for disease diagnosis, treatment, and prevention. Here, we provide a high-resolution view of the dynamics between host and gut microbiota during antibiotic-induced intestinal microbiota depletion, opportunistic Salmonella typhimurium and Clostridium difficile pathogenesis, and recovery from these perturbed states in a mouse model. Host-centric proteome and microbial community profiles provide a nuanced longitudinal view, revealing the interdependence between host and microbiota in evolving dysbioses. Time- and condition-specific molecular and microbial signatures are evident and clearly distinguished from pathogen-independent inflammatory fingerprints. Our data reveal that mice recovering from antibiotic treatment or C. difficile infection retain lingering signatures of inflammation, despite compositional normalization of the microbiota, and host responses could be rapidly and durably relieved through fecal transplant. These experiments demonstrate insights that emerge from the combination of these orthogonal, untargeted approaches to the gastrointestinal ecosystem.Host-Microbiota Interactions in the Pathogenesis of Antibiotic-Associated Diseases.Lichtman Joshua S JS, Ferreyra Jessica A JA, Ng Katharine M KM, Smits Samuel A SA, Sonnenburg Justin L JL, Elias Joshua E JESan, SAN, 2810441M03Rik, MeCN, nat5, NCMe, 1-(14)C-labeled, 3H-labeled, NAT13, Peptidomics, mak3, atado, NAT5P, ethanenitrile, CG12352, NAT13P, acetonitrile, Nat13, Thermo Scientific, sample population, hNAT5, san, solid, AW112078, hSAN, span., CH3-C#N, sample, DmelCG12352, Nat5, NAT5, methyl cyanide, Mak3, nat13, Chromatographies, ACETONITRILE, 2600005K24Rik, DmAAF34715, cyanomethane, Mak3p, MAK3antibiotic, host organism, Microbial Community Composition, other disease, Community Composition, disruption by symbiont of host cell, activation by organism of non-apoptotic programmed cell death in other organism, hemolysin activity, antibiotique, antimicrobials, regulation by symbiont of host system process, modulation by organism of defense response of other organism involved in symbiotic interaction, disorders, positive regulation by symbiont of host non-apoptotic programmed cell death, antimicrobial agents, Microbial, positive regulation by symbiont of host programmed cell death, Human, microbicides, enhancement of host programmed cell death, diseases, induction by organism of non-apoptotic programmed cell death in other organism during symbiotic interaction, hemolysis by symbiont of host RBCs, Diseases, modulation by symbiont of host system process, modulation by symbiont of host defense response, pathogenesis, disease or disorder, condition, microbicide, diseases and disorders, induction by organism of programmed cell death in other organism involved in symbiotic interaction, mitigation by symbiont of host defense response, Microbial Communities, haemolysis in host, antibiotics, upregulation by symbiont of host programmed cell death, Microbiome, antimicrobial, induction of non-apoptotic programmed cell death by other organism, modification by symbiont of host biological process, human disease, enhancement of host programmed cell death by organism, Microbiomes, stimulation by symbiont of host programmed cell death, Microbial Community Compositions, Microbial Community, Antibiotika, Microbial Community Structure, Community Structure, perturbation by symbiont of host defense response, induction by organism of programmed cell death in other organism during symbiotic interaction, activation by organism of programmed cell death in other organism during symbiotic interaction, modification by symbiont of host morphology or physiology, non-neoplastic, Composition, regulation of cytolysis of host cells by symbiont, disease, activation by organism of host programmed cell death, induction by symbiont of host programmed cell death, hemolysis by symbiont of host red blood cells, activation by symbiont of host programmed cell death, Microbial Community Structures, Microbiotas, disorder, Homo sapiens disease, medical condition., cytolysis by organism of host cells, associated, Human Microbiomes, Community, Human Microbiome, AntibiotikumBru, Gene Ontology Projects, Raw, Engrailed, determination, Ass-1, protein, Principal Component Analyses, L-(+)-glutamine, peptide, Polypeptides, L-Isomer Methionine, protein polypeptide chains, L-glutamine, Drug Tolerance, Methionine, L-Glutaminsaeure-5-amid, peptido, ClvPrd, AA408052, fold, Project, L-2-aminoglutaramic acid, 2, G-protein coupled receptor 13, Software Engineering, Analysis, protein aggregate, CD105, WMS, Computer Program, Mass Spectrum Analysis, DL-Asparagine, Svc, asparagina, peptides, asparagine, Analyses, fractalkine receptor, M, N, L-Asparagine, Open, D-Glutamine, Q, Computer Programs and Programming, V, proteins, ASN, CMK-BRL-1, Asn, ASS, GPR13, ppm, sample, S-endoglin, house mouse, GPHYSD2, Racemethionine, drug tolerance, SGS, AI662476, wide/broad, Data Set, immune system tolerance, T5E21.12, mouse, 2-Amino-4-(methylthio)butyric acid, Spectrum Analysis, Source Softwares, Software Tools, Programs, ACMICD, Spectroscopy, Program, Computer Applications, EnR, EN, en1, Algorithm, Computer Applications Software, Computer Applications Softwares, Immunologic Tolerance, Methionin, Ontology Projects, methionine, Hmet, Softwares, END, T5E21_12, L Glutamine, Eng, parent ion, Gene Ontologies, Ontology, Software Applications, Ontologies, En, Projects, mice, Source Software, Es, Spectrometry, MASS, 2-amino-3-carbamoylpropanoic acid, (S)-2, L-glutamic acid gamma-amide, wide, Applications, Principal Component, Self Tolerance, precursor ion, Tolerance, beta chemokine receptor-like 1, Mouse, Polypeptide, Liquimeth, Proteomes, Computer Software Applications, GLUTAMINE, 2-amino-4-(methylsulfanyl)butanoic acid, 5-diamino-5-oxopentanoic acid, L Isomer, FBN, Levoglutamide, Hasp, Gene, precursor, Spectrum Analyses, broad, Computer, (2S)-2-amino-4-carbamoylbutanoic acid, protein-containing complex, DmelCG9015, V28, Gene Ontology Project, C-X3-C CKR-1, Gene Ontology, Discriminant, CMK-BRL1, polypeptide chain, ECTOL1, Mass, Gene Products, L-Methionine, Endo, Del(8)44H, spa2, Pedameth, Mass Spectroscopy, Application, Open Source Softwares, (2S)-2, Software Application, Open Source Software, Engr, Computer Software Application, OCTD, Asparagin, AI528660, 2-amino-4-(methylthio)butanoic acid, 10^[-6], Tools, peptidos, L-Glutamine, metionina, chemokine receptor CX3CR1, HHT1, Applications Software, Engrailed/Invected, Gene., Open Source, data, CG9015, Computer Software, DL-Methionine, protein complex, Proteins, total expressed protein, L-2-Aminoglutaramic acid, function, backward, L-Isomer, Peptide, Tool, polypeptide, Software Tool, Experiment, Immune Tolerance, native protein, natural protein, Mus, Protein, chemical analysis, CMKBRL1, 153867_at, sequence, Glutamic acid 5-amide, MFS1, spt, L-Glutamin, Software, Mass Spectrum Analyses, Data Base, WMS2, Met, CX3CR1, Ontology Project, Mass Spectrum, Col4a-1, Glutamic acid amide, Engineering, 4-diamino-4-oxobutanoic acid, primary structure of sequence macromolecule, sample population, Protein Gene Products, Computer Programs, Gene Proteins, Applications Softwares, D Glutamine, Discriminant Analyses, SSKS, alpha-amino-gamma-methylmercaptobutyric acid, Peptid, Apa, assay, ORW1, reversed, Immunological TolerancePlantar Prints, host organism, Dys symbiosis, Plantar Print, Antemortem Diagnosis, Dysbioses, Inflammations, antimicrobials, Laboratory, Mus domesticus, Print, positive regulation by symbiont of host non-apoptotic programmed cell death, Infestations and Infections, antimicrobial agents, CASP-14, Visible Light, Diagnosis, House Mouse, Long Term, 12, Readability, microbicides, Clostridium difficile, diseases, hemolysis by symbiont of host RBCs, hnu, symptoms, pathogenesis, 2, diseases and disorders, 4, Ecological, Effect, foton, Dysbacterioses, antimicrobial, modification by symbiont of host biological process, human disease, inflammatory response, Salmonella enterica serovar Typhimurium, stimulation by symbiont of host programmed cell death, Antibiotika, Microbial Community Structure, alimentary tract, Swiss Mice, activation by organism of programmed cell death in other organism during symbiotic interaction, [5], g, Disbioses, Microbial Community Structures, digestive tube, Homo sapiens disease, asd, Plantar, Infections and Infestations, cytolysis by organism of host cells, house mouse, alimentary system, Long-Term Effects, Ecologic Systems, Diagnose, Disbacterioses, gamma, antibiotic, close to, screening, Radiation, lower gastrointestinal tract, mouse, Longterm Effect, Light, Niche, Microbial, positive regulation by symbiont of host programmed cell death, Diagnoses, Postmortem, LIGHT, enhancement of host programmed cell death, Examinations and Diagnoses, Mini-ICE, Diseases, modulation by symbiont of host system process, microbicide, Postmortem Diagnosis, Microbial Communities, haemolysis in host, Visible Radiations, Diagnoses and Examination, Mus musculus, Postmortem Diagnoses, Ecologic, AI747421, Visible Radiation, Ecosystems, HVEML, Caspase-14 subunit p10, Microbial Community Compositions, mice, System, Swiss Mouse, perturbation by symbiont of host defense response, signs, Infection and Infestation, Caspase-14 subunit p19, MICE, induction by organism of programmed cell death in other organism during symbiotic interaction, modification by symbiont of host morphology or physiology, domesticus, Composition, disease, regulation of cytolysis of host cells by symbiont, light quantum, induction by symbiont of host programmed cell death, gastrointestinal system, hemolysis by symbiont of host red blood cells, activation by symbiont of host programmed cell death, Disbiosis, Mouse, Innate, Proteomes, time, Human Microbiomes, :i:1, Community, 12:i:1, 3.4.22.-, other disease, digestive canal, Microbial Community Composition, Inflammatory Response, Habitats, Salmonella typhi-murium, antibiotique, Effects, regulation by symbiont of host system process, modulation by organism of defense response of other organism involved in symbiotic interaction, enteric tract, mini-ICE, Human, Ly113, period, Gus, Gur, Gut, induction by organism of non-apoptotic programmed cell death in other organism during symbiotic interaction, House, disease or disorder, Mus musculus domesticus, light, Antemortem, Mice, Bacillus typhimurium, antibiotics, upregulation by symbiont of host programmed cell death, induction of non-apoptotic programmed cell death by other organism, Fingerprints, gut, Longterm, Swiss, Lichtquant, Biome, inflammation, Diagnoses and Examinations, Long-Term, Visible, Habitat, non-neoplastic, Infestation and Infection, Biomes, Innate Inflammatory Response, lower GI tract, Ecological System, photon, disorder, Long-Term Effect, TR2, Dys-symbiosis, Prints, Human Microbiome, Antibiotikum, Antemortem 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Community Structure, Gus-t, Gus-s, Gus-r, House Mice, Understanding, Ecological Systems, [Clostridium] difficile, Longterm Effects, LTg, Laboratory Mice, Disbacteriosis, Salmonella enterica subsp. enterica serovar 1, Dys-symbioses, activation by organism of host programmed cell death, Photoradiations, approaches, Innate Inflammatory Responses, vicinity of, Microbiotas, Salmonella typhimurium LT2, Ecological Niche, Laboratory MousePlantar Prints, host organism, Dys symbiosis, Plantar Print, Antemortem Diagnosis, Dysbioses, Inflammations, antimicrobials, Laboratory, Mus domesticus, Print, positive regulation by symbiont of host non-apoptotic programmed cell death, Infestations and Infections, antimicrobial agents, CASP-14, Diagnosis, House Mouse, Long Term, 12, Readability, microbicides, Clostridium difficile, diseases, hemolysis by symbiont of host RBCs, symptoms, pathogenesis, 2, diseases and disorders, 4, Ecological, Effect, Dysbacterioses, antimicrobial, modification by symbiont of host biological process, human disease, inflammatory response, Salmonella enterica serovar Typhimurium, stimulation by symbiont of host programmed cell death, Antibiotika, Microbial Community Structure, alimentary tract, Swiss Mice, activation by organism of programmed cell death in other organism during symbiotic interaction, [5], g, Disbioses, Microbial Community Structures, digestive tube, Homo sapiens disease, asd, Plantar, Infections and Infestations, cytolysis by organism of host cells, house mouse, alimentary system, Long-Term Effects, Ecologic Systems, Diagnose, Disbacterioses, antibiotic, close to, screening, lower gastrointestinal tract, mouse, Longterm Effect, Niche, Microbial, positive regulation by symbiont of host programmed cell death, Diagnoses, Postmortem, enhancement of host programmed cell death, Examinations and Diagnoses, Mini-ICE, Diseases, modulation by symbiont of host system process, microbicide, Postmortem Diagnosis, Microbial Communities, haemolysis in host, 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Dys-symbioses, activation by organism of host programmed cell death, approaches, Innate Inflammatory Responses, vicinity of, Microbiotas, Salmonella typhimurium LT2, Ecological Niche, Laboratory Mouseantibiotic, host organism, Microbial Community Composition, other disease, Community Composition, disruption by symbiont of host cell, activation by organism of non-apoptotic programmed cell death in other organism, hemolysin activity, antibiotique, antimicrobials, regulation by symbiont of host system process, modulation by organism of defense response of other organism involved in symbiotic interaction, Streptomycin Grünenthal, disorders, positive regulation by symbiont of host non-apoptotic programmed cell death, antimicrobial agents, Strepto Fatol, medical condition, Microbial, positive regulation by symbiont of host programmed cell death, Human, microbicides, Streptomycin Sulfate, enhancement of host programmed cell death, diseases, induction by organism of non-apoptotic programmed cell death in other organism during symbiotic interaction, Strepto-Fatol, Streptomycin Sulphate, hemolysis by symbiont of host RBCs, Diseases, modulation by symbiont of host system process, modulation by symbiont of host defense response, pathogenesis, disease or disorder, condition, Strepto Hefa, microbicide, diseases and disorders, Streptomycine Panpharma, induction by organism of programmed cell death in other organism involved in symbiotic interaction, mitigation by symbiont of host defense response, Microbial Communities, Estreptomicina Normon, haemolysis in host, antibiotics, upregulation by symbiont of host programmed cell death, Microbiome, O-2-deoxy-2-(methylamino)-alpha-L-glucopyranosyl-(1-2)-O-5-deoxy-3-C-formyl-alpha-L-lyxofuranosyl-(1-4)-N, antimicrobial, induction of non-apoptotic programmed cell death by other organism, modification by symbiont of host biological process, human disease, enhancement of host programmed cell death by organism, Microbiomes, D-Streptamine, stimulation by symbiont of host programmed cell death, Microbial Community Compositions, Streptomycin Sulfate (2:3) Salt, N'-bis(aminoiminomethyl)-, Microbial Community, Antibiotika, Microbial Community Structure, Community Structure, perturbation by symbiont of host defense response, induction by organism of programmed cell death in other organism during symbiotic interaction, activation by organism of programmed cell death in other organism during symbiotic interaction, Samonella., modification by symbiont of host morphology or physiology, non-neoplastic, Composition, regulation of cytolysis of host cells by symbiont, disease, Estreptomicina CEPA, Strepto-Hefa, activation by organism of host programmed cell death, induction by symbiont of host programmed cell death, hemolysis by symbiont of host red blood cells, Estreptomicina Clariana, activation by symbiont of host programmed cell death, Microbial Community Structures, Microbiotas, disorder, Homo sapiens disease, cytolysis by organism of host cells, associated, Human Microbiomes, Community, Human Microbiome, Antibiotikum471trueHost-microbiota interactions in the pathogenesis of antibiotic-associated diseases:Streptomycin plus SalmonellaImproved understanding of the interplay between host and microbes stands to illuminate new avenues for disease diagnosis, treatment and prevention. Here, we provide a high-resolution view of the dynamics between host and gut microbiota during antibiotic induced intestinal microbiota depletion, opportunistic Salmonella typhimurium and Clostridium difficile pathogenesis, and recovery from these perturbed states in a mouse model. Host-centric proteome and microbial community profiles provide an unprecedented longitudinal view revealing the interdependence between host and microbiota in evolving dysbioses. Time- and condition-specific molecular and microbial signatures are evident and clearly distinguished from pathogen-independent inflammatory fingerprints. Our data reveal that mice recovering from antibiotic treatment or C. difficile infection retain lingering signatures of inflammation despite compositional normalization of the microbiota, and host responses could be rapidly and durably relieved through fecal transplant. These experiments define a novel platform for combining orthogonal, untargeted approaches to shed new light on the gastrointestinal ecosystem.2016-02-042015-11-05PXD003152280655164609918049829535851114513335244224942024527872842188090368093270429330845811363336351524260119834300662758385NCBITaxon:12806888856189611143011872635555711452623649346136403195206512695736664923916197467073853883641135461582158231066568895390531136364762721123294422291180992323122586365458333460792519365914320597129386558195851149315242592637371250232NCBITaxon:12721119577481866148858431043002451358672256807617554373592540816918045426683429531945305861266835149822505814963674452158554528113208147956410039237514636942049433208964208963445974137979138712728384400667203275453293529367156759388036478434643867716052165994048321659721659545501315282693042165915627161696833916243218321729204277944762376454317203094980197525556978159509439843948840479NCBITaxon:2157525338551531051067439899037122857759515205968762262311210884555588845587077918178081736309431796758144571698936160488409859NCBITaxon:371621047826794015059071483643204210613204913816936303555432046632633311994565453511025411103217459216129264201288676410026420369456941016763410210761277351524867131658239254727933428146135843014172987609174633457744491675476048932128735675684030135062191726518130194111929439367110411310239320255598632582788396591047594120347495109716049016529983552566366817585439801102432608663102459808757417555183201964471452680457966313670190832331156114155355104219325552113834397634981812359871069955529NCBITaxon:4751850298335476113615741465477180066556484337677144137929976798251021699823897641400820840741400821137351155711089725482444474153NCBITaxon:50557899698446752510003646534933414714749354801946751299114359741276473137086326547876565893639835322159589366983819201110677577271034819852348780265554479464098609958615718717668599191572951372211711012929210768783497419860202809392499148840633424923423515233598598865591324974649987039202111072943311711393635272159874190850371170827117082841823502414511396929319021978224746360461471237472269402375939723287581722532566481219071905079452659600131972211915853101774208588596NCBITaxon:615750521028307989515586411051989972375059576131720002634196102641088878176179212190659407121906772275885815689964975151950582873757244NCBITaxon:22023717NCBITaxon:170361220199985705060506172407476792745062724915961533355418400524643213686150596487844612286662941786661347515363291018194301086731018510184NCBITaxon:1763573039635586331492862876705801321650852718481865368595105135553482260710185687294296110091416333NCBITaxon:619184023210007348824123363630710470058127187878645159812894555663577553470951451225786425011449447260704NCBITaxon:13356262607052607076584574054163677483167233150561007133705654195NCBITaxon:305550445791399878168119011928752829126806315327341478281055524NCBITaxon:960613585846900811116781502283051930283672859300852900561742NCBITaxon:5693826883064017946991510118499526225435258759131515901448242838111394422584416041937047592721204414370860423281677285035158199011951953267386370137024924053608838581622488186156227748817562615835583715333760572671193501998086119350216787910857913711371272407190650371475917262981288057125627457572709030903113335503728142433747924910078711082NCBITaxon:96157243359463318586260799141262200298492670NCBITaxon:12637192812492125283038568385695911692661006581373523756127504542666255151978813566383750644223360094129349790546322455525363524721401257515115199764990851515143899237453747445446415243235937605920222887051580595536555088157932716029385157811497863389229382894535936479437509173NCBITaxon:685441275422511775299159010901341673871589552101296610306129671585158451584937659393432715910022637673388914792359046142345128768959119833296646704146479293657616428034116022164133159928038280353690910891768814989462181214108034817939228788929502711313329528282944568617493468191126526997227321890382107601247190400727159736997828114311402064119810871355477436581424507229533796982042321242231291632180334708714537209164573321535815754626694040137992877702020603281143193382935508332912922114864374572526499972830357390871830872672710379085507176299707678926837041557372921405365138829412816078395639243142626548982273775611559620732208659588273555169360533079725518113549143213715974953502611595561432138406072587814144733521509493349194963401614334728005936046316461046607629033815184547448500356709747726566977195124017484185560133575554792042741580536076994688103762014887329726100594120037582890931643542826831425685007123038399001389464940838283594144242322197857742171598921409212205853939621157781154756929793244704749906604162103591905158114452749907312987779913112273170187546991103589915NCBITaxon:3729610360983341871049113079813367953164072994671034015786582645303337330638301130641399253064236365059116965478854698112116203431765261610337286129940445862073401153571119529652611745531114716133865413131663430552132312017983602532373127612552329935129938505731631764261979401151345844577267872862321933415134618620862116079139222798351681196125522814953932232311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