Thegutmicrobiome:ConnectingspatialorganizationtofunctionCarolinaTropini1,*,KristenA.Earle1,*,KerwynCaseyHuang1,2,†,andJustinL.Sonnenburg2,†1DepartmentofMicrobiologyandImmunology,StanfordUniversitySchoolofMedicine,Stanford,CA94305,USA2DepartmentofBioengineering,StanfordUniversity,Stanford,CA94305,USAAbstractThefirstrudimentaryevidencethatthehumanbodyharborsamicrobiotahintedatthecomplexityofhost-associatedmicrobialecosystems.Now,almost400yearslater,arenaissanceinthestudyofmicrobiotaspatialorganization,drivenbycoincidentrevolutionsinimagingandsequencingtechnologies,isrevealingfunctionalrelationshipsbetweenbiogeographyandhealth,particularlyinthevertebrategut.Inthisreview,wepresentourcurrentunderstandingofprinciplesgoverningthelocalizationofintestinalbacteria,andspatialrelationshipsbetweenbacteriaandtheirhosts.Wefurtherdiscussimportantemergingdirectionsthatwillenableprogressingfromtheinherentlydescriptivenatureoflocalizationand–omicstechnologiestoprovidefunctional,quantitative,andmechanisticinsightintothiscomplexecosystem.IntroductionThecomplexconsortiumofmicrobesthatinhabitsthedistalhumanguthasbecomeatopicofintensescientificstudyoverthepastdecade,resultinginhugegainsofsequence-based,molecular,andfunctionalunderstanding.Still,manyofthegoverningprinciplesbywhichthehumanbodyactsasahometomicrobiallifewereestablishedbypioneeringresearchfromseveralhundredyearsago.Inthe17thcentury,AntonievanLeeuwenhoekcreatedlensespowerfulenoughtoobservebacteriaforthefirsttime,andquicklyfocusedonhisownbody.Inscrapingsfromtheplaquebetweenhisteeth,hefoundadiverse,abundantarrayof“animalcules”.Nevertheless,itwasnotuntilthe20thcenturythatElieMetchnikoffelucidatedthathumansarebornsterileandthenpopulatedimmediatelyafterbirthbynumerousmicrobes(Metchnikoff,1901),andlaidoutanatlasforthegastrointestinaltract†Correspondenceto:JustinSonnenburg(jsonnenburg@stanford.edu)orKerwynCaseyHuang(kchuang@stanford.edu).*AuthorscontributedequallyAuthorContributionsJ.S.,K.C.H,C.T.,andK.E.contributedtotheconcep...
