2024
Microbial transformation of dietary xenobiotics shapes gut microbiome composition
Culp E, Nelson N, Verdegaal A, Goodman A. Microbial transformation of dietary xenobiotics shapes gut microbiome composition. Cell 2024, 187: 6327-6345.e20. PMID: 39321800, PMCID: PMC11531382, DOI: 10.1016/j.cell.2024.08.038.Peer-Reviewed Original ResearchGut microbiomeHuman gut microbesGut microbiome compositionDiet-microbiome interactionsGut microbesCommunity compositionMicrobiome compositionMicrobial metabolismResponse to dietInterindividual variationMicrobiomeDietary xenobioticsMap interactionsGutMetabolic activityEnzymeXenobioticsDetoxificationGenesMicrobesResveratrolRemodelingTraitsInteractionVariationIntegrating the gut microbiome and pharmacology
Verdegaal A, Goodman A. Integrating the gut microbiome and pharmacology. Science Translational Medicine 2024, 16: eadg8357. PMID: 38295186, DOI: 10.1126/scitranslmed.adg8357.Peer-Reviewed Original Research
2023
Gut microbes modulate (p)ppGpp during a time-restricted feeding regimen
Ontai-Brenning A, Hamchand R, Crawford J, Goodman A. Gut microbes modulate (p)ppGpp during a time-restricted feeding regimen. MBio 2023, 14: e01907-23. PMID: 37971266, PMCID: PMC10746209, DOI: 10.1128/mbio.01907-23.Peer-Reviewed Original ResearchMetformin inhibits digestive proteases and impairs protein digestion in mice
Kelly C, Verdegaal A, Anderson B, Shaw W, Bencivenga-Barry N, Folta-Stogniew E, Goodman A. Metformin inhibits digestive proteases and impairs protein digestion in mice. Journal Of Biological Chemistry 2023, 299: 105363. PMID: 37863262, PMCID: PMC10663847, DOI: 10.1016/j.jbc.2023.105363.Peer-Reviewed Original ResearchConceptsGastrointestinal side effectsSide effectsDrug concentrationsDaily metformin doseFirst-line therapyType 2 diabetesEnteropeptidase activityPrescribed medicationsMetformin doseIntestinal lumenGastrointestinal tissuesMice exhibitMetforminProtein maldigestionHuman duodenumProtein digestionTrypsin activityDigestive enzymesMedicationsDiabetesMaldigestionDuodenumTherapyActivityMiceInfection leaves a genetic and functional mark on the gut population of a commensal bacterium
Tawk C, Lim B, Bencivenga-Barry N, Lees H, Ramos R, Cross J, Goodman A. Infection leaves a genetic and functional mark on the gut population of a commensal bacterium. Cell Host & Microbe 2023, 31: 811-826.e6. PMID: 37119822, PMCID: PMC10197903, DOI: 10.1016/j.chom.2023.04.005.Peer-Reviewed Original ResearchConceptsRapid genetic adaptationSingle nucleotide variantsMultiple phylaGenetic adaptationFunctional marksStable marksEnteric infectionsGene expressionPopulation dynamicsGut commensalsCommensal populationsMicrobiome compositionAbsence of infectionRapid selectionCitrobacter rodentiumFitnessGut populationsCommensal bacteriumInfected miceGastrointestinal infectionsGnotobiotic miceCommensalGut lumenDirect administrationVitamin B6Cross-feeding in the gut microbiome: Ecology and mechanisms
Culp E, Goodman A. Cross-feeding in the gut microbiome: Ecology and mechanisms. Cell Host & Microbe 2023, 31: 485-499. PMID: 37054671, PMCID: PMC10125260, DOI: 10.1016/j.chom.2023.03.016.Peer-Reviewed Original ResearchConceptsHost healthHost-microbe interactionsSpecies fitnessMicrobe-microbeEvolutionary implicationsMicrobial inhabitantsGut communitiesTrophic networksMicrobial communitiesTrophic levelsMammalian gutPrimary fermentersMetabolic outputDifferent microbesAmino acidsGut commensalsCooperative interactionsGut microbiomeNegative interactionsFitnessMutualismEcologyMicrobesEmergent roleCofactorBacteria require phase separation for fitness in the mammalian gut
Krypotou E, Townsend G, Gao X, Tachiyama S, Liu J, Pokorzynski N, Goodman A, Groisman E. Bacteria require phase separation for fitness in the mammalian gut. Science 2023, 379: 1149-1156. PMID: 36927025, PMCID: PMC10148683, DOI: 10.1126/science.abn7229.Peer-Reviewed Original ResearchConceptsMammalian gutTranscription termination factor RhoTermination factor RhoGene regulationTranscription terminationMechanisms bacteriaBacteria interactionsHuman commensalValuable targetBacteriaRhoGut microbiotaFitnessNovel clinical applicationsTherapeutic manipulationGutHuman healthCommensalRegulation
2022
Gut colonization by Bacteroides requires translation by an EF‐G paralog lacking GTPase activity
Han W, Peng B, Wang C, Townsend G, Barry N, Peske F, Goodman A, Liu J, Rodnina M, Groisman E. Gut colonization by Bacteroides requires translation by an EF‐G paralog lacking GTPase activity. The EMBO Journal 2022, 42: embj2022112372. PMID: 36472247, PMCID: PMC9841332, DOI: 10.15252/embj.2022112372.Peer-Reviewed Original ResearchConceptsEF-G1Protein synthesisGTPase activityGuanosine triphosphateElongation factor GCarbon starvationCellular processesStarvation conditionsBacteroides thetaiotaomicronFactor GSingular abilityAmino acidsCell growthParalogsMurine cecumTranslocationGut colonizationColonizationCellsRibosomesProteinStarvationThetaiotaomicronBacteriaFitness
2019
Mapping human microbiome drug metabolism by gut bacteria and their genes
Zimmermann M, Zimmermann-Kogadeeva M, Wegmann R, Goodman AL. Mapping human microbiome drug metabolism by gut bacteria and their genes. Nature 2019, 570: 462-467. PMID: 31158845, PMCID: PMC6597290, DOI: 10.1038/s41586-019-1291-3.Peer-Reviewed Original ResearchConceptsHuman gut bacteriaGut bacteriaHigh-throughput genetic analysisMicrobial gene productsDiverse cladeGene contentGenomic contentGene productsGenetic analysisMolecular mechanismsDrug metabolismBacteriaMultiple disease indicationsMetabolic activityDrug-metabolizing activityGut microbiomeMicrobiomeMetabolismDrug developmentMedical therapyTreatment delayMass spectrometryCladeDisease indicationsAdverse effectsSeparating host and microbiome contributions to drug pharmacokinetics and toxicity
Zimmermann M, Zimmermann-Kogadeeva M, Wegmann R, Goodman AL. Separating host and microbiome contributions to drug pharmacokinetics and toxicity. Science 2019, 363 PMID: 30733391, PMCID: PMC6533120, DOI: 10.1126/science.aat9931.Peer-Reviewed Original ResearchConceptsMicrobiome contributionDrug metabolismFunction of bioavailabilityDrug-metabolizing activitySame metabolic transformationsMetabolism of drugsSystemic drugsMetabolite exposureMetabolite absorptionGut microbiotaDrug pharmacokineticsDrug efficacyPharmacokinetic modelDrugsMedical drugsTransit kineticsMetabolismInterpersonal variationMetabolic transformationToxicityMetabolic routesPharmacokineticsMiceWhen gut bacteria spoil drug treatment
Zimmermann M, Zimmermann-Kogadeeva M, Goodman A. When gut bacteria spoil drug treatment. TheScienceBreaker 2019, 05 DOI: 10.25250/thescbr.brk262.Commentaries, Editorials and Letters
2018
Human gut Bacteroides capture vitamin B12 via cell surface-exposed lipoproteins
Wexler AG, Schofield WB, Degnan PH, Folta-Stogniew E, Barry NA, Goodman AL. Human gut Bacteroides capture vitamin B12 via cell surface-exposed lipoproteins. ELife 2018, 7: e37138. PMID: 30226189, PMCID: PMC6143338, DOI: 10.7554/elife.37138.Peer-Reviewed Original ResearchThe Stringent Response Determines the Ability of a Commensal Bacterium to Survive Starvation and to Persist in the Gut
Schofield WB, Zimmermann-Kogadeeva M, Zimmermann M, Barry NA, Goodman AL. The Stringent Response Determines the Ability of a Commensal Bacterium to Survive Starvation and to Persist in the Gut. Cell Host & Microbe 2018, 24: 120-132.e6. PMID: 30008292, PMCID: PMC6086485, DOI: 10.1016/j.chom.2018.06.002.Peer-Reviewed Original ResearchConceptsCarbon starvationStringent responseHuman gut bacterium Bacteroides thetaiotaomicronTricarboxylic acid cycle genesMultiple biosynthetic pathwaysCycle genesCentral metabolismMammalian gutTriggers accumulationBiosynthetic pathwayBacteroides thetaiotaomicronDeficient strainMetabolic regulatorAlpha-ketoglutarate supplementationStarvationAlpha-ketoglutarateC labelingCommensal bacteriaMetabolomic analysisGut microbiomeCommensal bacteriumThetaiotaomicronBacteriaPathwayGutSpontaneous translocation of a human enterococcal gut pathobiont drives systemic autoimmunity
Vieira S, Hiltensperger M, Kumar V, Zegarra-Ruiz D, Dehner C, Barbieri A, Jain D, Goodman A, Kriegel M. Spontaneous translocation of a human enterococcal gut pathobiont drives systemic autoimmunity. The Journal Of Immunology 2018, 200: 162.10-162.10. DOI: 10.4049/jimmunol.200.supp.162.10.Peer-Reviewed Original ResearchHost-microbiota interactionsOral vancomycin treatmentInduction of autoantibodiesPlasmacytoid dendritic cellsMesenteric lymph nodesPathogenesis of autoimmunityE. gallinarumAutoimmune hepatitisTfh cellsLupus patientsOrgan manifestationsPathogenic autoantibodiesDendritic cellsLymph nodesCytokines IFNGut barrierVancomycin treatmentC57BL/6 animalsSystemic autoimmunityInduction of moleculesLiver tissueAutoimmunityAhR pathwayBarrier functionMucus layer
2017
Autoantibody cross-reactivity with a microbial protein from a prevalent human gut commensal in antiphospholipid syndrome
ruff W, Roth A, Dehner C, Vieira S, Goodman A, Kriegel M. Autoantibody cross-reactivity with a microbial protein from a prevalent human gut commensal in antiphospholipid syndrome. The Journal Of Immunology 2017, 198: 58.4-58.4. DOI: 10.4049/jimmunol.198.supp.58.4.Peer-Reviewed Original ResearchAntiphospholipid syndromeAPS patientsGut commensalsBALB/cJ miceMajor B-cell epitopeGut commensal bacteriaAnti-B2GPI antibodiesB-cell epitopesInfectious triggerAutoantibody productionIgG autoantibodiesAntigenic sourceUnknown etiologyAutoantibody reactivityControl antibodyCell epitopesGut microbiotaCommensal bacteriaMajor autoantigenLow titersAutoantibodiesHuman stoolMonoclonal antibodiesVivo studiesPersistent stimulusAn insider's perspective: Bacteroides as a window into the microbiome
Wexler AG, Goodman AL. An insider's perspective: Bacteroides as a window into the microbiome. Nature Microbiology 2017, 2: 17026. PMID: 28440278, PMCID: PMC5679392, DOI: 10.1038/nmicrobiol.2017.26.Peer-Reviewed Original ResearchConceptsGut bacteriumHuman gut BacteroidesModel organismsMicrobial communitiesMetagenome sequencesGut BacteroidesClose relativesGut microorganismsEscherichia coliCommensal microorganismsCentury of studyBacteriumMicroorganismsGut microbiotaImportant insightsBacteroidesSheer diversityHuman healthGenomicsEcologyOrganismsEcosystemsDiversityMicrobiomeColiEngineered Regulatory Systems Modulate Gene Expression of Human Commensals in the Gut
Lim B, Zimmermann M, Barry NA, Goodman AL. Engineered Regulatory Systems Modulate Gene Expression of Human Commensals in the Gut. Cell 2017, 169: 547-558.e15. PMID: 28431252, PMCID: PMC5532740, DOI: 10.1016/j.cell.2017.03.045.Peer-Reviewed Original ResearchConceptsGene expressionModulate gene expressionAbsence of inducerCommunity assemblyAddition of inducerGenetic toolsInducible promoterGene productsExpression platformHost physiologyPromoter activityHuman commensalGenus BacteroidesSynthetic inducersGut anaerobesInducerSialidase activityExpressionNumerous aspectsGut microbiotaSialic acidGutPromoterValuable toolCommensalAutoantigen‐specific T and B Cell Cross‐reactivity to a Gut Commensal in Antiphospholipid Syndrome
Dehner C, Ruff W, Vieira S, Goodman A, Kriegel M. Autoantigen‐specific T and B Cell Cross‐reactivity to a Gut Commensal in Antiphospholipid Syndrome. The FASEB Journal 2017, 31 DOI: 10.1096/fasebj.31.1_supplement.184.7.Peer-Reviewed Original ResearchBALB/c miceAdaptive immune systemAntiphospholipid syndromeB cellsC miceT cellsCell epitopesImmune systemPathogenic T cell epitopesTetramer-positive T cellsCD4 memory T cellsMemory T cellsTNF-α ILAdaptive immune responsesT cell clonesT cell epitopesDose-responsive mannerHuman commensal bacteriumB-cell epitopesEpitope-specific monoclonal antibodiesIL-21Patient PBMCsLymph nodesGPI antibodiesAntigenic challengeCommensal Ro60 Orthologs as Persistent Triggers of Human Lupus
Dehner C, Greiling T, Chen X, Renfroe S, Hughes K, Vieira S, Ruff W, Boccitto M, Sim S, Chen X, Kriegel C, Degnan P, Goodman A, Wolin S, Kriegel M. Commensal Ro60 Orthologs as Persistent Triggers of Human Lupus. The FASEB Journal 2017, 31 DOI: 10.1096/fasebj.31.1_supplement.55.3.Peer-Reviewed Original ResearchMesenteric lymph nodesSystemic lupus erythematosusT cell clonesLupus patientsSLE patientsTg miceAutoimmune diseasesMicrobial triggersCell clonesT cellsGerm-free (GF) C57BL/6 miceP. propionicumMemory CD4 T cellsHuman SLE seraPrototypical autoimmune diseaseCD4 T cellsHuman autoimmune diseasesGerm-free miceAnti-Ro60 antibodiesEarliest autoantibodiesRo60 antibodiesLupus modelsLupus erythematosusLymph nodesHuman lupus
2016
Lupus T and B cell cross-reactivity between the human Ro60 autoantigen and Ro60 orthologs from the human microbiota
Greiling T, Dehner C, Renfroe S, Chen X, Vieira S, Ruff W, Goodman A, Wolin S, Kriegel M. Lupus T and B cell cross-reactivity between the human Ro60 autoantigen and Ro60 orthologs from the human microbiota. The Journal Of Immunology 2016, 196: 124.16-124.16. DOI: 10.4049/jimmunol.196.supp.124.16.Peer-Reviewed Original ResearchLupus patientsAnti-Ro60 antibodiesB cellsP. propionicumGerm-free miceGut commensalsHuman lupus patientsHuman microbiotaT cell clonesNovel therapeutic approachesSubset of skinAutoimmune TEarliest autoantibodiesLupus TRo60 antibodiesIgA antibodiesChronic autoimmunityMemory TSystemic autoimmunityHealthy controlsT cellsTherapeutic approachesPatientsSusceptible individualsAutoimmunity