TheGutMicrobiomeandInflammation

Kanneboyina Nagaraju, DVM, PhDProfessor and Founding Chair

Department of Pharmaceutical sciencesSchool of Pharmacy and Pharmaceutical Sciences

Binghamton University,State University of New York

Binghamton, NY, USA

What is the Microbiome

• Collective genomes of microbial flora harbored by humans

• Microfloraisthecommunityofmicroorganisms,includingalgae,fungi,andbacteriathatliveinoronanotherlivingorganismorinaparticularhabitat

• Theratiooftheamountofmicrobestocellsinourbodiesis10:1• MostidentifiedDNAsequencesfloatinginourbloodplasmabelongtoviruses• Wearemorethemthanweareus

http://linxc10.wixsite.com/microbes/the-microbiome

TheMicrobiome

Depictionofthehumanbodyandbacteriathatpredominate

GriceandSerge2011

GriceandSerge2011

SkinhistologywithmicroorganismsEcosystem:

Functio

nsofm

icrobiota

YoungVB2017

PrebioticNutrientsthatfavorthegrowthandpredominanceofbeneficialmicrobesandtheirinherentfunctions.Mostofthesehavebeencarbohydratesthatcannotbebrokendownbythehumandigestivemachinerybutaremetabolizedbyspecificmembersofthemicrobiota

ProbioticCommonlydefinedas“livemicro-organismswhich,whenadministeredinadequateamounts,conferahealthbenefitonthehost.”Inthepast,thesewereoftenorganismsthatwerefirstrecognizedinfermentedfoodproducts.Currently,thereisinterestinidentifyingpotentialprobioticsthataremembersofthemicrobiotaofhealthypeople

YoungVB2017

Alldiseasesbegininthegut

HippocratesTheFatherofWesternMedicine

460BC-370BC

Thebacterialcellsharboredwithinthehumangastrointestinaltract(GIT)outnumberthehost’scellsbyafactorof10andthegenesencodedbythebacteriaresidentwithintheGIToutnumbertheirhost’sgenesbymorethan100times.

Approximately100trillionmicro-organismsinthegut

BullandPlummer2014

Roleofthe

gutm

icrobiotainhealth

and

dise

ase

Valdesetal.,2018

Compositionandluminalnumbersofdominantmicrobialspeciesinthehumangastrointestinaltract.

SartorandMazmanian 2012

• Lowerbacterialdiversityhasbeenreproduciblyobservedinpeoplewithinflammatoryboweldisease, psoriaticarthritis, type1diabetes, atopiceczema, coeliacdisease, obesity,type2diabetes, andarterialstiffness, thaninhealthycontrols.

• Germ-free mice that receive faecal microbes from obese humans gain more weight than mice that receive microbes from healthy weight humans

Thegutmicrobiotaanddiseases

IBD:UlcerativeColitisandCrohn’sdiseaseColitisisreducedorabsentingermfreeanimalsandthosetreatedwithantibiotics

Moreinflammation

MorediseaseactivityShiftincomposition-perpetuationofthedisease

Shortchainfattyacids

Inflammation

Clementeetal.,2018

Arthritisisreducedorabsentingermfreeanimals

Clementeetal.,2018

Valdesetal.,2018

Valdesetal.,2018

Valdesetal.,2018

Valdesetal.,2018

Valdesetal.,2018

Consensusanduncertainties

Potentialstrategiesfortherapeuticmicrobiomemanipulation

Clementeetal.,2018