2023
Metformin 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 B6Bacteria 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 routesPharmacokineticsMice
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 bacteriumThetaiotaomicronBacteriaPathwayGut
2017
Engineered 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 toolCommensal
2016
Human symbionts inject and neutralize antibacterial toxins to persist in the gut
Wexler AG, Bao Y, Whitney JC, Bobay LM, Xavier JB, Schofield WB, Barry NA, Russell AB, Tran BQ, Goo YA, Goodlett DR, Ochman H, Mougous JD, Goodman AL. Human symbionts inject and neutralize antibacterial toxins to persist in the gut. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: 3639-3644. PMID: 26957597, PMCID: PMC4822603, DOI: 10.1073/pnas.1525637113.Peer-Reviewed Original ResearchConceptsHuman gut symbiontGut symbiontsMicrobial communitiesProminent Human Gut SymbiontHundreds of speciesHuman gut commensalGut microbial communityContact-dependent killingHuman gut microbiomeAntibacterial toxinsInterbacterial interactionsInteraction assaysCommunity compositionInterbacterial antagonismEffector lociImmunity genesMajor phylaSecretome studiesHuman symbiontsSymbiontsMicrobiome manipulationGut microbesGut commensalsMultiple mouse modelsGut microbiome
2015
Antimicrobial peptide resistance mediates resilience of prominent gut commensals during inflammation
Cullen TW, Schofield WB, Barry NA, Putnam EE, Rundell EA, Trent MS, Degnan PH, Booth CJ, Yu H, Goodman AL. Antimicrobial peptide resistance mediates resilience of prominent gut commensals during inflammation. Science 2015, 347: 170-175. PMID: 25574022, PMCID: PMC4388331, DOI: 10.1126/science.1260580.Peer-Reviewed Original Research
2011
Extensive personal human gut microbiota culture collections characterized and manipulated in gnotobiotic mice
Goodman AL, Kallstrom G, Faith JJ, Reyes A, Moore A, Dantas G, Gordon JI. Extensive personal human gut microbiota culture collections characterized and manipulated in gnotobiotic mice. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 6252-6257. PMID: 21436049, PMCID: PMC3076821, DOI: 10.1073/pnas.1102938108.Peer-Reviewed Original Research
2009
Identifying Genetic Determinants Needed to Establish a Human Gut Symbiont in Its Habitat
Goodman AL, McNulty NP, Zhao Y, Leip D, Mitra RD, Lozupone CA, Knight R, Gordon JI. Identifying Genetic Determinants Needed to Establish a Human Gut Symbiont in Its Habitat. Cell Host & Microbe 2009, 6: 279-289. PMID: 19748469, PMCID: PMC2895552, DOI: 10.1016/j.chom.2009.08.003.Peer-Reviewed Original ResearchConceptsHuman gut symbiontHuman gut bacteriumHuman gut commensalAdjacent chromosomal DNAGut symbiontsHuman gut microbiotaGenomic locationMicrobial genesCommunity compositionTransposon mutantsMicrobial adaptationChromosomal DNAHuman symbiontsParallel sequencingGut bacteriumBacteroides thetaiotaomicronRelative abundanceGenetic determinantsGut commensalsSymbiontsVivo selectionMetabolic organCellular compositionGnotobiotic miceGut microbiota