Geneticsandintestinalmicrobiomedeterminesusceptibilitytomultiplesclerosis

StudyinvolvingtheClusterofExcellence"PrecisionMedicineinChronicInflammation"showsthelinkbetweengenetics,intestinalmicrobiomeandmultiplesclerosisinmiceforthefirsttime.

Multiplesclerosis(MS)isanautoimmunediseaseofthenervoussystemwhichaffectsmorethantwomillionpeopleworldwide.Inthecourseofthedisease,theimmunesystemattackstheinsulationlayerofnervecells,andcentersofinflammationdevelopinthebrainandspinalcord,whichovertimecanleadtoseriousneurologicalsymptoms.TheexactcausesofMShavenotyetbeendetermined.Inadditiontogeneticpredisposition,viralinfectionsandalsoenvironmentalinfluencessuchasnutritionarethoughttoberesponsibleforMS.Thereisincreasingevidencethatthemicrobiomeoftheintestine,i.e.allofthemicroorganismslivinginthegut,playsaroleinmanyautoimmunediseasesandcouldalsobeacauseofMS.AGerman-AmericanresearchteaminvolvingProfessorHaukeBuschandDr.AxelKnstnerfromtheLbeckInstituteofExperimentalDermatology(LIED)attheUniversityMedicalCenterSchleswig-Holstein(UKSH),CampusLbeck,andtheUniversityofLbeck(UzL),bothmembersoftheClusterofExcellence"PrecisionMedicineinChronicInflammation"(PMI),hasnowsucceededindemonstratingarelationshipbetweenthemicrobiome,geneticsandmultiplesclerosisinmiceforthefirsttime. TheteamledbyDr.DimitryKrementsovfromtheUniversityofVermontrecentlypublishedtheresultsonlineintherenownedscientificjournalProceedingsoftheNationalAcademyofSciences(PNAS).

Intheirstudy,theresearcherswereabletoshowthatmicehaveadifferentsusceptibilitytoMSdependingontheirgeneticcharacteristics,whichisalsoinfluencedbytheintestinalmicrobiomeandthemetabolismoftheintestinalbacteria.Todoso,theyexaminedmicewhichareparticularlyaffectedbyMSduetoageneticpredisposition,andcomparedthemwithmicewhichareaffectedbyMStoalesserextentornotatallduetotheirgeneticpredisposition.InthemicrobiomewithsevereMS,theresearchersfoundanincreasedpresenceofthebacterialspeciesLactobacillusreuteri.

"Wethenwantedtofindoutwhetherthesebacteriaareonlypresentasaresultofthegeneticcharacteristics,orwhethertheythemselveshaveanimpactonthesusceptibilitytoMS,"saidProf.Busch,boardmemberoftheClusterofExcellencePMIandheadofthe"SystemsBiologyofInflammatoryDiseases"workinggroupatLIED.Toinvestigatethis,theresearcherstransferredsamplesoftheintestinalmicrobiome,i.e.bacterialmixtureswhichwereenrichedwithLactobacillusreuteri,aswellassampleswithoutthisenrichment,intomicewithouttheirownintestinalmicrobiome.ThemicrobiomeenrichedwithLactobacillusreuteriindeedledtoincreasedseverityofMSinthesemice."Wecouldthusdemonstratethattheintestinalbacteriathemselvesalsohaveaninfluenceontheseverityofthedisease,"saidBusch.

"Duetoitspositiveinfluenceondigestion,Lactobacillusreuteriisoftenusedasaprobiotic.Inourstudy,preciselythisbacteriumissurprisinglythe"badguy".Thisshowstheimportantrolethatnutrition,whichultimatelyalsoinfluencesthemicrobiome,couldplayinthepreventionandtreatmentofMS,"saidtheleadbioinformaticsscientistofthestudy,Dr.AxelKnstner,scientistinthe"SystemsBiologyofInflammatoryDiseases"workinggroupatLIEDandalsoamemberoftheClusterofExcellencePMI."Ourobservationsmakeclearhowimportantitisthatinadditiontogenetics,otherfactorssuchastheintestinalmicrobiomeandnutritionarealsoconsideredregardingtheoriginandprogressionofcomplexdiseasessuchasMS,"addedKnstner.

Scientificcontact:

Prof.HaukeBusch
LIED-LbeckInstituteofExperimentalDermatology
UniversityofLbeckandUKSH,CampusLbeck
+49451-3101-8470
hauke.busch@uni-luebeck.de

Dr.AxelKnstner
LIED-LbeckInstituteofExperimentalDermatology
UniversityofLbeckandUKSH,CampusLbeck
+49-451-3101-5475
axel.kuenstner@uni-luebeck.de

portrait photo
©SaschaKlahn

ProfessorHaukeBusch,steeringcommitteememberoftheClusterofExcellencePMIandheadoftheresearchgroup"SystemsBiology"attheInstituteforExperimentalDermatology(LIED)oftheUniversityMedicalCenterSchleswig-Holstein(UKSH),CampusLübeck,andtheUniversityofLübeck(UzL).

portrait photo
©privat

Dr.AxelKünstner,bioinformaticianattheInstituteforExperimentalDermatology(LIED)oftheUniversityMedicalCenterSchleswig-Holstein(UKSH),CampusLübeck,andtheUniversityofLübeck(UzL),andmemberoftheClusterofExcellence"PrecisionMedicineinChronicInflammation"(PMI).

 

Originalpublikation:

TheresaL.Montgomery,AxelKnstner,JosephineJ.KennedyaQianFang,LoriAsarian,RachelCulp-Hill,AngeloDAlessandro,CoryTeuscher,HaukeBusch,andDimitryN.Krementsov:InteractionsbetweenhostgeneticsandgutmicrobiotadeterminesusceptibilitytoCNSautoimmunity,PNAS(2020).https://doi.org/10.1073/pnas.2002817117

AbouttheClusterofExcellencePMI

TheClusterofExcellence"PrecisionMedicineinChronicInflammation"(PMI)isbeingfundedfrom2019to2025throughtheGermanExcellenceStrategy(ExStra).Itsucceedsthe"InflammationatInterfacesCluster,whichwasalreadyfundedintwoperiodsoftheExcellenceInitiative(2007-2018).Around300membersfromeightinstitutionsatfourlocationsareinvolved:Kiel(KielUniversity,UniversityMedicalCenterSchleswig-Holstein(UKSH),MuthesiusUniversityofFineArtsandDesign,KielInstitutefortheWorldEconomy(IfW),LeibnizInstituteforScienceandMathematicsEducation(IPN)),Lbeck(UniversityofLbeck,UniversityMedicalCenterSchleswig-Holstein(UKSH)),Pln(MaxPlanckInstituteforEvolutionaryBiology)andBorstel(ResearchCenterBorstel-LeibnizLungCenter).

Thegoalistotranslateinterdisciplinaryresearchfindingsonchronicinflammatorydiseasesofbarrierorganstohealthcaremoreintensively,aswellastofulfilpreviouslyunsatisfiedneedsofthepatients.Threepointsareimportantinthecontextofsuccessfultreatment,andarethereforeattheheartofPMIresearch:theearlydetectionofchronicinflammatorydiseases,thepredictionofdiseaseprogressionandcomplications,andthepredictionofindividualresponsestotreatment.

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FrederikeBuhse
PublicRelations,ExcellenceClusterPMI

ClusterofExcellence "PrecisionMedicineinChronicInflammation"
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