2024
Bile acid-gut microbiota imbalance in cholestasis and its long-term effect in mice
Yang X, Xu Y, Li J, Ran X, Gu Z, Song L, Zhang L, Wen L, Ji G, Wang R. Bile acid-gut microbiota imbalance in cholestasis and its long-term effect in mice. MSystems 2024, 9: e00127-24. PMID: 38934542, PMCID: PMC11265269, DOI: 10.1128/msystems.00127-24.Peer-Reviewed Original ResearchGut microbiotaGut microbiota dysbiosisDysregulated gut microbiotaGut microbiota transplantationGerm-free miceVirulence factorsSmall intestinal bacteriaBile acid homeostasisMicrobiota dysbiosisDecreased diversityMicrobiota imbalanceMicrobiotaMouse model of cholestasisBile acidsMouse modelIntestinal bacteriaAcid homeostasisMicrobiota transplantationClinical management of patientsGutHepatic bile acidsLong-term effectsPre-clinical findingsModel of cholestasisManagement of patientsGut microbiota from B-cell-specific TLR9-deficient NOD mice promote IL-10+ Breg cells and protect against T1D
Yang X, Huang J, Peng J, Wang P, Wong F, Wang R, Wang D, Wen L. Gut microbiota from B-cell-specific TLR9-deficient NOD mice promote IL-10+ Breg cells and protect against T1D. Frontiers In Immunology 2024, 15: 1413177. PMID: 38903498, PMCID: PMC11187306, DOI: 10.3389/fimmu.2024.1413177.Peer-Reviewed Original ResearchGut microbiotaGerm-free miceToll-like receptor 9Increased gut permeabilityIntestinal microbiotaGut permeabilityT1D developmentGut microbiota compositionFecal samplesTransferred to germ-free miceGut barrier integrityBreg cell differentiationMicrobiota influenceMucin degradationMicrobiota compositionBreg cellsAltered microbiotaMicrobiota impactMicrobiotaGene expressionImmune regulationDevelopment of T1DCell differentiationGutNOD miceTlr9 deficiency in B cells leads to obesity by promoting inflammation and gut dysbiosis
Wang P, Yang X, Zhang L, Sha S, Huang J, Peng J, Gu J, Pearson J, Hu Y, Zhao H, Wong F, Wang Q, Wen L. Tlr9 deficiency in B cells leads to obesity by promoting inflammation and gut dysbiosis. Nature Communications 2024, 15: 4232. PMID: 38762479, PMCID: PMC11102548, DOI: 10.1038/s41467-024-48611-8.Peer-Reviewed Original ResearchConceptsToll-like receptor 9Gut microbiotaGut microbial communityTransferred to germ-free miceB cellsGerm-free miceTLR9 deficiencyKO miceGene sequencesGerminal center B cellsMicrobial communitiesMarginal zone B cellsGut dysbiosisFollicular helper cellsSelf-DNAMetabolic homeostasisAssociated with increased frequencyPro-inflammatory stateFat tissue inflammationGutHigh-fat dietMicrobiotaHelper cellsT cellsControl miceGut microbiota and therapy for obesity and type 2 diabetes
Zhang L, Wang P, Huang J, Xing Y, Wong F, Suo J, Wen L. Gut microbiota and therapy for obesity and type 2 diabetes. Frontiers In Endocrinology 2024, 15: 1333778. PMID: 38596222, PMCID: PMC11002083, DOI: 10.3389/fendo.2024.1333778.Peer-Reviewed Original ResearchGut microbiota compositionGut microbiotaMicrobiota compositionType 2 diabetesFunction of gut microbiotaHomeostasis of gut microbiotaMicrobiota-based approachesModulating gut microbiotaBariatric surgeryEffective anti-obesity treatmentQuality of life of individualsMicrobiotaMildly obese patientsSustained weight lossAssociated with obesityDiminished quality of lifeAnti-obesity treatmentObesity management strategiesGutQuality of lifeNon-surgical interventionsIncreased medical costsPublic health crisisMusculoskeletal disordersObese patientsTLR5-deficiency controls dendritic cell subset development in an autoimmune diabetes-susceptible model
Pearson J, Hu Y, Peng J, Wong F, Wen L. TLR5-deficiency controls dendritic cell subset development in an autoimmune diabetes-susceptible model. Frontiers In Immunology 2024, 15: 1333967. PMID: 38482010, PMCID: PMC10935730, DOI: 10.3389/fimmu.2024.1333967.Peer-Reviewed Original ResearchConceptsToll-like receptor 5Antigen-presenting cellsDendritic cellsType 1 diabetesTLR5-deficientDC developmentCytokine secretionCD4<sup>+</sup> T cell proliferationPathogenesis of type 1 diabetesT cell responsesEnhanced cytokine secretionT cell proliferationWild-type miceSusceptibility to obesitySusceptibility to T1DProinflammatory cytokine secretionGut microbiotaSpontaneous T1DNOD miceAutoimmune diabetesNon-obeseHuman T1DReceptor 5Autoimmune diseasesHyper-secretion
2023
Distinct signatures of gut microbiota and metabolites in different types of diabetes: a population-based cross-sectional study
Hu J, Ding J, Li X, Li J, Zheng T, Xie L, Li C, Tang Y, Guo K, Huang J, Liu S, Yan J, Peng W, Hou C, Wen L, Xu A, Zhou Z, Xiao Y. Distinct signatures of gut microbiota and metabolites in different types of diabetes: a population-based cross-sectional study. EClinicalMedicine 2023, 62: 102132. PMID: 37593224, PMCID: PMC10430172, DOI: 10.1016/j.eclinm.2023.102132.Peer-Reviewed Original ResearchAdult-onset T1DHealthy controlsGut microbiotaT1D patientsShort-chain fatty acid-producing bacteriaPopulation-based cross-sectional studyGut microbial alterationsRecent epidemiological dataType 1 diabetesCross-sectional studyT2D patientsIntestinal disturbancesDifferential diagnosisSerum metabolitesEpidemiological dataPatientsStudy subjectsT1DDiabetesSignificant differencesAcid-producing bacteriaMicrobiotaMicrobial profilesNational Key ResearchMicrobial alterationsDifferences in clinical features and gut microbiota between individuals with methamphetamine casual use and methamphetamine use disorder
He L, Yang B, Ma Y, Wen L, Liu F, Zhang X, Liu T. Differences in clinical features and gut microbiota between individuals with methamphetamine casual use and methamphetamine use disorder. Frontiers In Cellular And Infection Microbiology 2023, 13: 1103919. PMID: 36909722, PMCID: PMC9996337, DOI: 10.3389/fcimb.2023.1103919.Peer-Reviewed Original ResearchConceptsMA use disorderClinical featuresGut microbiotaWithdrawal symptomsMA usersEnterotype 2Use disordersGM diversityBody mass indexMethamphetamine use disorderSemi-Structured AssessmentMass indexNeuropsychiatric symptomsHigh incidenceDiagnostic criteriaDifferential microbesDistinct enterotypesDrug dependenceGM differencesSymptomsClinical traitsPerformed network analysisStrong cravingsFecal samplesFurther studiesNLRP6 deficiency expands a novel CD103+ B cell population that confers immune tolerance in NOD mice
Pearson J, Peng J, Huang J, Yu X, Tai N, Hu Y, Sha S, Flavell R, Zhao H, Wong F, Wen L. NLRP6 deficiency expands a novel CD103+ B cell population that confers immune tolerance in NOD mice. Frontiers In Immunology 2023, 14: 1147925. PMID: 36911699, PMCID: PMC9995752, DOI: 10.3389/fimmu.2023.1147925.Peer-Reviewed Original ResearchConceptsNlrp6-deficient miceType 1 diabetesNLRP6 deficiencyB cellsIL-10Non-obese diabetic (NOD) miceType 1 diabetes developmentRole of NLRP6Germ-free miceT cell proliferationB cell populationsIntestinal epithelial cellsBreg populationAutoimmune diabetesNOD miceCrohn's diseaseImmune toleranceDiabetes developmentDiabetic miceImmune cellsCD103Inflammasome proteinsImmune responseNLRP6Gut microbiota
2022
Correction: Toll-like receptor 9 deficiency induces osteoclastic bone loss via gut microbiota-associated systemic chronic inflammation
Ding P, Tan Q, Wei Z, Chen Q, Wang C, Qi L, Wen L, Zhang C, Yao C. Correction: Toll-like receptor 9 deficiency induces osteoclastic bone loss via gut microbiota-associated systemic chronic inflammation. Bone Research 2022, 10: 47. PMID: 35798700, PMCID: PMC9263109, DOI: 10.1038/s41413-022-00221-0.Peer-Reviewed Original ResearchToll-like receptor 9 deficiency induces osteoclastic bone loss via gut microbiota-associated systemic chronic inflammation
Ding P, Tan Q, Wei Z, Chen Q, Wang C, Qi L, Wen L, Zhang C, Yao C. Toll-like receptor 9 deficiency induces osteoclastic bone loss via gut microbiota-associated systemic chronic inflammation. Bone Research 2022, 10: 42. PMID: 35624094, PMCID: PMC9142495, DOI: 10.1038/s41413-022-00210-3.Peer-Reviewed Original ResearchToll-like receptorsSystemic chronic inflammationBone lossGut microbiotaSystemic inflammationChronic inflammationBone metabolismLow-grade systemic chronic inflammationActivation of TLRsInflammation-induced osteoclastogenesisOsteoclastic bone lossExpansion of CD4Low bone massSubsequent bone lossInflammatory cytokinesBone massT cellsInflammationOsteoclast differentiationBone marrowMyeloid-biased hematopoiesisImmune systemHematopoietic stem cellsSingle-cell RNA sequencingMiceIgM-associated gut bacteria in obesity and type 2 diabetes in C57BL/6 mice and humans
Pearson JA, Ding H, Hu C, Peng J, Galuppo B, Wong FS, Caprio S, Santoro N, Wen L. IgM-associated gut bacteria in obesity and type 2 diabetes in C57BL/6 mice and humans. Diabetologia 2022, 65: 1398-1411. PMID: 35587276, PMCID: PMC9283171, DOI: 10.1007/s00125-022-05711-8.Peer-Reviewed Original ResearchConceptsFecal microbiota transplantType 2 diabetesNormal glucose toleranceB6 miceWild-type miceGlucose toleranceIgM antibodiesObese youthGut microbiotaWeight gainGut bacteriaObese young individualsImpaired glucose toleranceDiet-induced obesityConclusions/interpretationOur resultsBody weight gainGreater weight gainMice fecal microbiotaHuman stool samplesGlucose intoleranceClinical featuresC57BL/6 miceMicrobiota transplantRecipient miceStool samples
2021
IL-10 Deficiency Accelerates Type 1 Diabetes Development via Modulation of Innate and Adaptive Immune Cells and Gut Microbiota in BDC2.5 NOD Mice
Huang J, Tan Q, Tai N, Pearson JA, Li Y, Chao C, Zhang L, Peng J, Xing Y, Zhang L, Hu Y, Zhou Z, Wong FS, Wen L. IL-10 Deficiency Accelerates Type 1 Diabetes Development via Modulation of Innate and Adaptive Immune Cells and Gut Microbiota in BDC2.5 NOD Mice. Frontiers In Immunology 2021, 12: 702955. PMID: 34394099, PMCID: PMC8362616, DOI: 10.3389/fimmu.2021.702955.Peer-Reviewed Original ResearchConceptsNOD miceProportion of neutrophilsT cellsGut microbiotaDiabetes developmentT cell-mediated destructionT cell receptor transgenicType 1 diabetes developmentAccelerated diabetes developmentInhibition of diabetesModulation of InnatePathogenicity of CD4Cell-mediated destructionAdaptive immune cellsObese diabetic miceT regulatory (Treg) cellsDevelopment of diabetesPrevention of diabetesActivation of CD4Modulation of neutrophilsType 1 diabetesGut microbiota compositionInsulin-producing β-cellsSevere insulitisSpontaneous diabetes
2020
Gut microbial metabolites alter IgA immunity in type 1 diabetes
Huang J, Pearson JA, Peng J, Hu Y, Sha S, Xing Y, Huang G, Li X, Hu F, Xie Z, Xiao Y, Luo S, Chao C, Wong F, Zhou Z, Wen L. Gut microbial metabolites alter IgA immunity in type 1 diabetes. JCI Insight 2020, 5 PMID: 32298241, PMCID: PMC7259536, DOI: 10.1172/jci.insight.135718.Peer-Reviewed Original ResearchConceptsType 1 diabetesGut microbiotaNOD miceImmune responseGerm-free NOD miceIgA immune responseIgA-mediated immunityHealthy control subjectsPotential therapeutic agentShort-chain fatty acid productionIgA immunityT1D preventionIgA responsesControl subjectsDecreased severityT1DTherapeutic agentsFunctional effectsMicrobiotaDiabetesPatientsUnderlying mechanismMiceImmunitySCFA
2016
The Gut Microbiome in the NOD Mouse
Peng J, Hu Y, Wong FS, Wen L. The Gut Microbiome in the NOD Mouse. Methods In Molecular Biology 2016, 1433: 169-177. PMID: 27032947, DOI: 10.1007/7651_2016_331.Peer-Reviewed Original ResearchConceptsType 1 diabetes developmentNOD miceDiabetes developmentGut bacteriaSusceptible NOD miceNonobese diabetic (NOD) miceBacterial DNA sequencingGut microbiome compositionGut microbiome analysisMouse fecal samplesExcellent mouse modelDiabetic miceMouse modelGut microbiotaGut microbiomeIntestinal contentsMiceCritical modulatorDisease phenotypeFecal samplesMicrobiome compositionStandard protocolMicrobiome analysisHealthPathogenic microorganisms
2015
Maternal Antibiotic Treatment Protects Offspring from Diabetes Development in Nonobese Diabetic Mice by Generation of Tolerogenic APCs
Hu Y, Peng J, Tai N, Hu C, Zhang X, Wong FS, Wen L. Maternal Antibiotic Treatment Protects Offspring from Diabetes Development in Nonobese Diabetic Mice by Generation of Tolerogenic APCs. The Journal Of Immunology 2015, 195: 4176-4184. PMID: 26401004, PMCID: PMC4765177, DOI: 10.4049/jimmunol.1500884.Peer-Reviewed Original ResearchConceptsNOD miceTolerogenic APCsDiabetes developmentT cell-mediated autoimmune diseaseDiabetogenic CD8 T cellsCell-mediated autoimmune diseasePolymyxin BCD8 T cellsNonobese diabetic (NOD) miceType 1 diabetesHost immune systemIslet β-cellsAutoimmune diabetesDifferent time pointsImmune toleranceDiabetic miceAutoimmune diseasesProfound protectionT cellsImmune responseProtective effectCommensal microbiotaGut microbiotaSusceptible individualsCommensal bacteriaThe role of gut microbiota in the development of type 1, type 2 diabetes mellitus and obesity
Tai N, Wong FS, Wen L. The role of gut microbiota in the development of type 1, type 2 diabetes mellitus and obesity. Reviews In Endocrine And Metabolic Disorders 2015, 16: 55-65. PMID: 25619480, PMCID: PMC4348024, DOI: 10.1007/s11154-015-9309-0.Peer-Reviewed Original ResearchConceptsGut microbiotaAutoimmune type 1 diabetesType 2 diabetes mellitusInsulin-resistant type 2 diabetesMajor public health concernAltered gut microbiotaDevelopment of T1DType 2 diabetesType 1 diabetesGut microbiota compositionPublic health concernDiabetes mellitusPersistent hyperglycemiaMetabolic disordersRodent modelsMicrobiota compositionType 1ObesityDiabetesHealth concernPotential mechanismsMicrobiotaT2DT1DDisease development
2014
Long term effect of gut microbiota transfer on diabetes development
Peng J, Narasimhan S, Marchesi JR, Benson A, Wong FS, Wen L. Long term effect of gut microbiota transfer on diabetes development. Journal Of Autoimmunity 2014, 53: 85-94. PMID: 24767831, PMCID: PMC4361177, DOI: 10.1016/j.jaut.2014.03.005.Peer-Reviewed Original ResearchConceptsNOD miceGut microbiotaWild-type NOD miceNon-obese diabetic (NOD) miceGut microbiomeMyD88-deficient miceMucosal immune systemOnset of diabetesCD8αβ T cellsType 1 diabetesGut microbiota transferWeeks of ageAutoimmune diabetesT1D developmentDiabetes developmentDiabetic miceMicrobiota transferT cellsLamina propriaLong-term effectsProbiotic treatmentImmune systemLarge intestineDiabetesMice