2025
Activity of GPCR-targeted drugs influenced by human gut microbiota metabolism
Wu Q, Song D, Zhao Y, Verdegaal A, Turocy T, Duncan-Lowey B, Goodman A, Palm N, Crawford J. Activity of GPCR-targeted drugs influenced by human gut microbiota metabolism. Nature Chemistry 2025, 17: 808-821. PMID: 40181149, DOI: 10.1038/s41557-025-01789-w.Peer-Reviewed Original ResearchConceptsGut commensal bacteriaCommensal bacteriaGut microbial communityGut microbiota metabolismDrug metabolismMetabolize drugsMicrobial communitiesIndividual speciesMetabolic modeMorganella morganiiMicrobiota metabolismGPCR-targeted drugsTricyclic systemThiophene motifsBacteria mixtureBacteriaMetabolomics investigationsMetabolismTargeting GPCRsDrug metabolitesPharmacological efficacyDrug transformationDrug structureDrugMetabolitesTranslocating gut pathobiont Enterococcus gallinarum induces TH17 and IgG3 anti-RNA–directed autoimmunity in mouse and human
Gronke K, Nguyen M, Fuhrmann H, Santamaria de Souza N, Schumacher J, Pereira M, Löschberger U, Brinkhege A, Becker N, Yang Y, Sonnert N, Leopold S, Martin A, von Münchow-Klein L, Pessoa Rodrigues C, Cansever D, Hallet R, Richter K, Schubert D, Daniel G, Dylus D, Forkel M, Schwinge D, Schramm C, Redanz S, Lassen K, Manfredo Vieira S, Piali L, Palm N, Bieniossek C, Kriegel M. Translocating gut pathobiont Enterococcus gallinarum induces TH17 and IgG3 anti-RNA–directed autoimmunity in mouse and human. Science Translational Medicine 2025, 17: eadj6294. PMID: 39908347, DOI: 10.1126/scitranslmed.adj6294.Peer-Reviewed Original ResearchConceptsSystemic lupus erythematosusAutoimmune diseasesToll-like receptor 8Gut pathobiontsHuman adaptive immune responseLong-term sequelaeAdaptive immune responsesHuman T cellsChronic autoimmune diseaseHuman monocyte activationContribution to autoimmunityAutoimmune hepatitisAutoantibody titersAnti-<i>E.Autoimmune pathophysiologyLupus modelT-helperLifelong immunosuppressionTargeted therapyT cellsDisease activityLupus erythematosusAutoantibody responseMonocyte activationImmune response
2024
Mucosal sugars delineate pyrazine vs pyrazinone autoinducer signaling in Klebsiella oxytoca
Hamchand R, Wang K, Song D, Palm N, Crawford J. Mucosal sugars delineate pyrazine vs pyrazinone autoinducer signaling in Klebsiella oxytoca. Nature Communications 2024, 15: 8902. PMID: 39406708, PMCID: PMC11480411, DOI: 10.1038/s41467-024-53185-6.Peer-Reviewed Original ResearchConceptsK. oxytocaGeneral carbohydrate metabolismVirulence factor productionPLP-dependent enzymesAssociated with gutEnterobactin biosynthesisAutoinducer signalBacterial virulenceKlebsiella oxytocaSpecific carbohydratesHost immune responseCarbohydrate metabolismAutoinducerMolecular signalsVirulenceHistamine receptor H4BiosynthesisHost signalAcquisition responsesProtease inhibitorsPathwayHostLung pathologyLung isolationImmune responseThe human CD47 checkpoint is targeted by an immunosuppressive Aedes aegypti salivary factor to enhance arboviral skin infectivity
Marin-Lopez A, Huck J, Esterly A, Azcutia V, Rosen C, Garcia-Milian R, Sefik E, Vidal-Pedrola G, Raduwan H, Chen T, Arora G, Halene S, Shaw A, Palm N, Flavell R, Parkos C, Thangamani S, Ring A, Fikrig E. The human CD47 checkpoint is targeted by an immunosuppressive Aedes aegypti salivary factor to enhance arboviral skin infectivity. Science Immunology 2024, 9: eadk9872-eadk9872. PMID: 39121194, PMCID: PMC11924945, DOI: 10.1126/sciimmunol.adk9872.Peer-Reviewed Original ResearchConceptsSuppress antiviral responsesArthropod proteinsPathogen replicationAntiviral responseProtein AVertebrate hostsMosquito salivary proteinsUp-regulatedBlood feedingHuman macrophagesPleomorphic effectsSkin infectionsZika virus disseminationInhibit proinflammatory responsesSalivary proteinsProteinNatural ligandWhite blood cellsHuman skin explantsProinflammatory responseMosquito salivaVirus disseminationHuman CD47Salivary factorsArbovirus infection
2023
Highly multiplexed bioactivity screening reveals human and microbiota metabolome-GPCRome interactions
Chen H, Rosen C, González-Hernández J, Song D, Potempa J, Ring A, Palm N. Highly multiplexed bioactivity screening reveals human and microbiota metabolome-GPCRome interactions. Cell 2023, 186: 3095-3110.e19. PMID: 37321219, PMCID: PMC10330796, DOI: 10.1016/j.cell.2023.05.024.Peer-Reviewed Original Research
2022
Commensal microbiota from patients with inflammatory bowel disease produce genotoxic metabolites
Cao Y, Oh J, Xue M, Huh WJ, Wang J, Gonzalez-Hernandez JA, Rice TA, Martin AL, Song D, Crawford JM, Herzon SB, Palm NW. Commensal microbiota from patients with inflammatory bowel disease produce genotoxic metabolites. Science 2022, 378: eabm3233. PMID: 36302024, PMCID: PMC9993714, DOI: 10.1126/science.abm3233.Peer-Reviewed Original ResearchConceptsColorectal cancerInflammatory bowel disease patientsBowel disease patientsInflammatory bowel diseaseIndigenous gut microbesBowel diseaseDisease patientsCommensal microbiotaDNA damageColon tumorigenesisElicit DNA damageGut microbesGenotoxic metabolitesGut commensalsMorganella morganiiPatientsGenotoxic chemicalsDiseaseMicrobiotaMetabolitesGenotoxicityCancerMiceFull spectrumDamageWithin-host evolution of a gut pathobiont facilitates liver translocation
Yang Y, Nguyen M, Khetrapal V, Sonnert ND, Martin AL, Chen H, Kriegel MA, Palm NW. Within-host evolution of a gut pathobiont facilitates liver translocation. Nature 2022, 607: 563-570. PMID: 35831502, PMCID: PMC9308686, DOI: 10.1038/s41586-022-04949-x.Peer-Reviewed Original ResearchConceptsHost evolutionGene expression programsCell wall structureNon-synonymous mutationsComparative genomicsIndependent lineagesExperimental evolutionExpression programsDivergent evolutionRegulatory genesBacterial behaviorCritical regulatorBacterial translocationGut commensalsTranslocationE. gallinarumMesenteric lymph nodesInitiation of inflammationImmune evasionWall structureEvade DetectionMucosal nicheLactobacillus reuteriCommensalGut microbiotaInterspecies commensal interactions have nonlinear impacts on host immunity
Rice TA, Bielecka AA, Nguyen MT, Rosen CE, Song D, Sonnert ND, Yang Y, Cao Y, Khetrapal V, Catanzaro JR, Martin AL, Rashed SA, Leopold SR, Hao L, Yu X, van Dijk D, Ring AM, Flavell RA, de Zoete MR, Palm NW. Interspecies commensal interactions have nonlinear impacts on host immunity. Cell Host & Microbe 2022, 30: 988-1002.e6. PMID: 35640610, PMCID: PMC9283318, DOI: 10.1016/j.chom.2022.05.004.Peer-Reviewed Original ResearchConceptsImmunological outcomesCell activationIntestinal epithelial cell activationInflammatory bowel disease patientsBowel disease patientsDendritic cell activationMesenteric lymph nodesSystemic antibody responsesEpithelial cell activationImmunological milieuLymph nodesAntibody responseDisease patientsAkkermansia muciniphilaGnotobiotic miceHost immunityCommensal microbesHuman cohortsHuman gut bacteriaGut bacteriaMiceAllobaculumMuciniphilaDiseaseIncomplete penetrance
2020
Autoreactivity in naïve human fetal B cells is associated with commensal bacteria recognition
Chen JW, Rice TA, Bannock JM, Bielecka AA, Strauss JD, Catanzaro JR, Wang H, Menard LC, Anolik JH, Palm NW, Meffre E. Autoreactivity in naïve human fetal B cells is associated with commensal bacteria recognition. Science 2020, 369: 320-325. PMID: 32675374, DOI: 10.1126/science.aay9733.Peer-Reviewed Original ResearchConceptsB cell toleranceB cellsCell toleranceEarly human fetal lifeHuman fetal B cellsPolyreactive B cellsHuman fetal lifeApoptotic cellsFetal B cellsHuman fetal liverB cell specificitySingle B cellsAbundant autoantibodiesGut microbiota assemblyNewborn seraFetal lifeBone marrowFetal developmentHealthy adultsCommensal bacteriaRepertoire breadthMicrobiota assemblyFetal liverPreimmune repertoireCell specificity
2019
A Forward Chemical Genetic Screen Reveals Gut Microbiota Metabolites That Modulate Host Physiology
Chen H, Nwe PK, Yang Y, Rosen CE, Bielecka AA, Kuchroo M, Cline GW, Kruse AC, Ring AM, Crawford JM, Palm NW. A Forward Chemical Genetic Screen Reveals Gut Microbiota Metabolites That Modulate Host Physiology. Cell 2019, 177: 1217-1231.e18. PMID: 31006530, PMCID: PMC6536006, DOI: 10.1016/j.cell.2019.03.036.Peer-Reviewed Original ResearchConceptsHost physiologyBioactive microbial metabolitesHuman gut bacteriaHost sensingProlific producersG proteinsGut microbiota metabolitesBlood-brain barrierL-PheMicrobial metabolitesOrphan GPCRsGut bacteriaColonic motilityInhibitor administrationMicrobiota metabolitesIntestinal microbiotaSmall moleculesDietary histidineBacteriaPhysiologyMicrobiota metabolomeMetabolitesGPR97Orthogonal approachGPCRs
2014
Immunoglobulin A Coating Identifies Colitogenic Bacteria in Inflammatory Bowel Disease
Palm NW, de Zoete MR, Cullen TW, Barry NA, Stefanowski J, Hao L, Degnan PH, Hu J, Peter I, Zhang W, Ruggiero E, Cho JH, Goodman AL, Flavell RA. Immunoglobulin A Coating Identifies Colitogenic Bacteria in Inflammatory Bowel Disease. Cell 2014, 158: 1000-1010. PMID: 25171403, PMCID: PMC4174347, DOI: 10.1016/j.cell.2014.08.006.Peer-Reviewed Original ResearchConceptsInflammatory bowel diseaseBowel diseaseIgA coatingIntestinal microbiotaIntestinal bacteriaGerm-free miceIBD patientsIntestinal diseaseImmunoglobulin AMouse modelDiseaseAnaerobic culturingDramatic susceptibilityTargeted eliminationDisease developmentDisease susceptibilityMiceCell sortingMicrobiotaBacterial cell sortingFecal bacteriaSuch bacteriaColitisPatientsIgA
2012
Allergic host defences
Palm NW, Rosenstein RK, Medzhitov R. Allergic host defences. Nature 2012, 484: 465-472. PMID: 22538607, PMCID: PMC3596087, DOI: 10.1038/nature11047.Peer-Reviewed Original Research
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