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• Vaginal bacterial communi0es are thought create and maintain a lowenvironmental pH that restricts the growth of non‐indigenouspopula0ons.
• We sought to assess the stability of vaginal bacterial communi0es andmodeltemporaldynamics.
• 33 asymptoma0c, reproduc0ve‐age women self‐collected mid‐vaginalswabs every third day for 16 weeks as part of a vaginal douchingcessa0onstudy.(Brotmanetal.AmJObstetGynecol2008)
• Bacterial community composi0on was determined based on 16S rRNAgenesequences(V1‐V2region).
• A dataset of more than 2.97 million 16S rRNA gene sequences wasobtainedfrom988samples(29.9±1.6(SD)samplespersubject)withanaverage of 3,005 ± 1257 (SD) sequences per sample. Taxonomicassignmentswere performed as described by Ravel et al. (PNAS 2010)usingacombina0onoftheRDPclassifierandSpeciateIT.
• A linearmixed effectmodel for the log of Jensen‐Shannon divergencerate of community change was used to inves0gate the role ofmenstrua0on and sexual ac0vity on the constancy of the vaginalmicrobiota.Themodelaccountedforcorrela0onsbetweensamplesfromthe same par0cipant and was adjusted for 0me‐varying confoundersincluding vaginal douching, contracep0ve and normalized menstrualcycle0me.
• COMMUNITYSTATETYPE:Astatetypeiscomprisedofsamplesthathavesimilarbacterialspeciescomposi0on.Inthisstudyfivecommunitystatetypes were iden0fied. Profiles of community state types weredeterminedforeachwoman.
• COMMUNITYSTATECLASS:Acommunitystateclassisformedofsimilarcommunitystateprofiles.
• Thespeciescomposi+onofbacterialcommuni+esinsomewomenchangedmarkedlyovershortperiodsof+mewhileinothersitwasrela+velystable.
• Modelingofvaginalbacterialcommunitydynamicsindicatesthatcommunitystabilitywasassociatedwith+meinthemenstrualcycle,andvariedamongcommuni+esthatdifferedincomposi+on.
• Abe?erunderstandingoffactorsthatleadtothedevelopmentandmaintenanceofspecificandstablevaginalcommuni+esisneededsostrategiescanbedevelopedtopromoteandmaintainreproduc+vehealth.
• Infutureworkwewilldetermineifhabitsandprac+ces(includinguseoflubricants,feminine hygiene products, and specific sexual behaviors) influence communitydynamics.
1DepartmentofBiologicalSciences,UniversityofIdaho,Moscow,Idaho,USA,2Ini+a+veforBioinforma+csandEvolu+onaryStudies(IBEST),UniversityofIdaho,Moscow,Idaho,USA,3DepartmentofEpidemiologyandPublicHealth,UniversityofMarylandSchoolofMedicine,Bal+more,Maryland,USA,4Ins+tuteforGenomeSciences,UniversityofMarylandSchoolofMedicine,Bal+more,Maryland,USA,5DepartmentofMathema+cs,UniversityofIdaho,
Moscow,ID,USA,6DepartmentofSta+s+cs,UniversityofIdaho,Moscow,ID,USA,7DepartmentofMicrobiologyandImmunology,UniversityofMarylandSchoolofMedicine,Bal+more,Maryland,USA
RoxanaJ.Hickey1,2,RebeccaM.Brotman3,4,PawelGajer4,JoyceSakamoto4,SaraS.K.Koenig4,LiFu4,XiaZhou1,2,ZaidAbdo2,5,6,JacquesRavel4,7,LarryJ.Forney1,2
Temporal dynamics of vaginal bacterial communities
Figure1. Heatmapofphylotyperela0ve abundance from all 998samples longitudinally collectedfrom 33 women. Each ver0callinerepresentsonesample.
Three of the community state typeswere dominated by Lactobacillus sp.andrepresented17%(communitystatetype I), 6% (community state type II)and 41% (community state type III) ofthe samples. A total of 36% of thesamples did not contain significantnumber of Lactobacillus species(communitystatetypeIV‐AandIV‐B).
Figure 2. Dynamics of vaginalcommunity state types in 33womenover16weeks.
A. Dendrogram of distancesbetweenpropor+onsof thefivecommunity state within awomanover+me.
B. Heatmap of propor+ons ofcommunity state typesmeasuredwithin awoman over+me.
C. Color bar indica+ng communityclass (DA, LC, LG,DB, and LI) asdefined by clusters ofpropor+ons of community statetypeswithinawomanover+me.
D. Temporal profiles of communitystate types for 33 women over16 weeks. Each +me point isrepresented by a color‐codedcommunity state type assignedtothecorrespondingcommunitystate.
E. Box plot of Nugent scores foreachwomanover16weeks.
Figure3.Vaginalcommunitydynamics.
Panels(A)and(C).Subject21and2‐Interpolatedbargraphsofphylotypesabundance.Metadataandprofileofcommunitystatestypesareshownbelow.
Panels(B)and(D).Schema+csofthedynamicsofvaginalcommuni+esofsubject21and2inthevaginalcommunityspaceasdefinedbyRaveletal.(PNAS2010).
Figure 4. Examples of vaginalbacterial community that exhibitlowdynamics.
Communitydynamicsarerepresentedbyaheatmap(top)andaninterpolatedbargraphofphylotypesabundance(middle).The bo?om panel shows the rate ofchange of the Jensen‐Shannondivergence, and selected metadata,includingmensesandsexualac+vi+es.
Figure5.Examplesofvaginalbacterialcommunitythatexhibithighdynamics.(SeelegendFig.4)
ThisworkwassupportedbygrantsUH2AI083264andK01AI080974fromtheNa+onalIns+tuteofAllergyandInfec+ousDiseases,Na+onalIns+tutesofHealth.
• Itisthemostcommonmemberofvaginalcommuni+esamongwomenofallethnicgroups.
• L. iners has the smallest genome (~1.3Mb) of all known Lactobacillus sp.;appears to have undergone dras+cgenomereduc+on(Macklaimetal.PNAS2010). The genomes of other vaginalLactobacillus sp. range from ~1.6 – 2.3Mb.
• Genomic featuresofL. iners: incompleteTCA cycle; missing genes include thoserequired for synthesis of vitamins,cofactors,aminoacidsandpurines.
• IsL.inersdependentontheirneighborsforgrowthandsurvival–isthereanecologicalnetworkbasedonnutri+onal dependencies?Whatdisrupts thesecommunitynetworks?
• Aredifferencesincommunitycomposi+onrelevanttodifferencesincommunitystability?
WhyisL.inersofinterest? Communitynetworks,ecologicalresistanceandresilience
Walker’s“Driver‐PassengerModel”• One or more species “drive” the community; the
remainder are not essen+al for communityperformanceandmayvary.
• We postulate that lac+c acid bacteria drive thevaginalecosystem
L.iners
Species1
Species2
Species3
Species4
Species5
?
RESEARCHAIMS1. Gain a be?er understanding of the strain
diversity of L. iners in the vagina. Are theredifferences in the metabolic capabili+es orecologicalfunc+onsofstrains?
2. Iden+fy and characterize ecological networksof bacteria that L. iners may depend on forsurvivalandpersistence.
FrequencyorDura0on
DisturbedEcosystem
Intensity
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