3 Gut Bacteria

8/20/2019 3 Gut Bacteria

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3. Gut Microbes:

How They Help us OutStephanie Senef Wise Traditions Workshop

Nov. 8, 2013

eople.csail.mit.edu/senef/W!"#Slides#2013/3#$ut#%acteri


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Outline

• 'ut %acteria under sie$e

• (n&ection) novel perspective

•

(n*uen+a• Natural resistance and anti%iotics

• Summar


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'ut -acteria nder Sie$e


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Gut Bacteria and Health*

• We are an ecosstem) a communit o&

interactin$ cells – Trillions o& %acteria live in our %od

– The outnum%er our on cells 10)1

– illin$ them of ma make us sick or &at

•

8 million micro%ial $enes in our %odies3 million in di$estive sstem&rom more than1000 species4

• The pla ver essential roles in our %odies

– 5i$est &oods, a%sor% nutrients, provideen+mes, make vitamins and

antiin*ammatories

– 6e$ulate appetite and %rain &unction

• 7a$inal %irth mattersN!6;s /20/%ac


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“Our microbes are under threat— and the enemy is us*

•

?@icro%iomeA – BBC o& them are %eni$n or ofer protection

– Snthesi+e vitamins -12 and &olate

• -irth throu$h %irth canal v.s. D section4 –

(n&ant picks up motherEs micro%iome• Dolostrum provides &ood &or $ut %acteria

• (ndustriali+ed countries are too clean – 5rasticall altered micro%iome

• F. plori B0C G 10C in last hundred ears in .S.• sopha$eal cancer and childhood asthma have risen

in step

S+a%o, S Toda,/.usatoda.com/nes/health/stor/20120I13/%od%u$smicro%es/>2B


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H. pylori: There areBene!ts"*

• The Western orld has no si$niKcantlreduced the presence o& F. plori in the $ut – This has reduced the incidence o& stomach ulcers

and stomach cancer

– -ut it has also increased the incidence o&esopha$eal re*uL disease and esopha$eal cancer

• F. plori serve a use&ul role in reducin$ acidproduction % stomach) eLcess acida$$ravates the esopha$us

• We host a colon o& %acteria and the orkto$ether ith us &or a Mointl %eneKcial solution

:Daroline Fadle, @-< reports 7(5), 471-473, 2


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?


9/67:. Samsel and S. Senef, ntrop 2013, 1, 1J1>1J>

Glyphosate and the #hi$imate%athway*

• 'lphosate disrupts the shikimatepatha, leadin$ to ds%iosis o&aromatic amino acids

•

@onsanto claims $lphosate issa&e %ecause human cells don;thave the shikimate patha

• Foever, $ut %acteria are ver important to

human health, and the do have the patha• 5s%iosis in the $ut is increasin$l %ein$

reco$ni+ed as a &actor in modern diseases


10/67:. Samsel and S. Senef, ntrop 2013, 1, 1J1>1J>

Glyphosate and the #hi$imate%athway*

• 'lphosate disrupts the shikimatepatha, leadin$ to ds%iosis o&aromatic amino acids

•

@onsanto claims $lphosate issa&e %ecause human cells don;thave the shikimate patha

• Foever, $ut %acteria are ver important to

human health, and the do have the patha• 5s%iosis in the $ut is increasin$l %ein$

reco$ni+ed as a &actor in modern diseases

( ill have much moreto sa a%out this in

the section on$lphosate


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&eliac 'isease: an(pidemic*

• Deliac disease $luten intolerance4 is &oundthrou$hout the S at a rate o& up to 1 inever 133 persons, several orders o&

ma$nitude hi$her than previouslestimated

•


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?Time and time a$ain, e hear &rompatients that the never &elt depressedor anLious until the started

eLperiencin$ pro%lems ith their $ut.1I.asp


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&onnections Between the Gut andthe Brain*

.". Dran and T.'. 5inan, Nature 6evies Neuroscience 2012, I01I12.


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)ecapitulation

• Fealth $ut %acteria are essential to health

• 'lphosate 6oundup4 disrupts $ut %acteria

•

Deliac disease is a modern epidemic, likeldue to $lphosate more later4

• F. plori has %oth pros and cons

• The $ut%rain aLis links $ut %acterial

distress to neurolo$ical diseases


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(n&ection) Novel !erspective


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n+ection

(mpaired cholesterol sul&ate snthesis canlead to suscepti%ilit to in&ection, hich

introduces idespread patholo$

(n&ection serves a use&ul role inresupplin$ critical nutrients such as

co%alamin, &olate, and heparan sul&ate


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,ea$y Gut #yndrome*

: "rom http)//.precisionnutrition.com/alla%out$luten


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-ild #peculation

• Heak $ut and leak skin andleak %lood %rain %arrier lead

to inKltration o& micro%es&rom $ut or skin into %rain

• -acteria are ?luredA into the%od P into the %rain and

then killed and harvested torene important

nutrients• !ossi%le nutrients include)

– 7itamin -12 co%alamin4, vitamin -B &olate4,thiamine, vitamin and heparan sul&ate


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a auses ncreasen+ection

(mpaired Dholesterol Sul&ate SnthesisQ

@icro%es

@icro%es

@icro%es


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/drenalin #timulates BacterialGrowth*

• 7arious species $ron in culture%oth $ram ne$ative and $rampositive4

• drenalin added to mediumstimulated $roth

• Some species produce unknon

$rothenhancin$ stimulus inpresence o& adrenalin

– This can stimulate $roth o& other

species as ell:.S. inne et al., Hi&e Sciences >I 20004 30I


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#ul+ate 'epletion in&olitis *

• ''s in intestinal mucosa $reatl depleted insul&ate in association ith %oth colitis andDrohn;s disease – Dolitis) mostl ''s in luminal sur&ace

– Drohn;s) mostl ''s near %lood vessels

• Serum al%umin leaves vasculature andpenetrates intestinal linin$) – (nsuRcient ne$ative char$e results in eas access

• Serum al%umin depletion has severeconse9uences to %lood sta%ilit

: @urch et al., The Hancet 3J1)I11I1J, @ar 20, 1BB3


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#ul+ate 'epletion in&olitis *

• ''s in intestinal mucosa $reatl depleted insul&ate in association ith %oth colitis andDrohn;s disease – Dolitis) mostl ''s in luminal sur&ace

– Drohn;s) mostl ''s near %lood vessels

• Serum al%umin leaves vasculature andpenetrates intestinal linin$) – (nsuRcient ne$ative char$e results in eas access

• Serum al%umin depletion has severeconse9uences to %lood sta%ilit

: @urch et al., The Hancet 3J1)I11I1J, @ar 20, 1BB3

!eople ith colitis or Drohn;shave $reatl increased risk to

colon cancer


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,ea$y Gut

• 6educed sul&ate in the ''s in theintestines

• Dells are de&ective in transportin$ nutrients – Heads to severe vitamin deKciencies e.$., -124

• Ti$ht Munctions %eteen cells %ecome loose

• @icro%es can penetrate the $ut all andenter the %lood stream

– The can %e harvested % macropha$esQ


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Micro0illi in Gall Bladder(pithelium*

Fealth ne$ative char$e makes them stand tall

nhealth addition o& cationic polmer destros them

res 1 and 2 in uinton and !hilpott, O. Dell -iol. >, 1BI8, I


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Bacteria can #wim /cross GutBarrier"


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Microbial n0asionthrou1h BBB*

: "i$ure , p. 380, O..


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The Good #ide o+ n+ection andn2ammation in the Brain

• (n*ammation activates micro$lia topha$octose eat4 din$ cells andmloid %eta

• -acterial eLposure promotespha$octosis

• Both dying cells and acteria can e

recycled into ne! ra! "aterials# – $hese n%trients "ay e essential to rain

health


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/ %ossible &auseand(4ect)elationship

• "irst comes impaired %arriers, impairednutrient transport and impaired %loodcolloidal suspension

• Dertain nutrients are desperatel neededto KL the pro%lems) e.$., co%alamin,vitamin , heparan sul&ate – -acteria are invited in to provide those

nutrientsQ

• The disease ma %e uncom&orta%le, %utthe alternative ma %e orseQ

n+ection and


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: . Tu&ano et al., Semin Throm% Femost 2012384, 1

n+ection and/therosclerosis*


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-hat Happens i+ you Treatwith /ntibiotics*

. Tu&ano et al., Seminars in Throm%osis P Femostasis7ol. 384, 2012, 123


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-hat Happens i+ you Treatwith /ntibiotics*

. Tu&ano et al., Seminars in Throm%osis P Femostasis7ol. 384, 2012, 123

Si$niKcantl more people die o&cardiovascular disease &olloin$

anti%iotic treatment p0.014


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&hlamydia pneumoniae

• Dause pneumonia henthe in&ect the lun$s

• Sho up &re9uentl in

cardiovascular pla9ue• Sho up &re9uentl in

l+heimer;s pla9ue

&hat are they doing there'''


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&hlamydia %roduce Heparan#ul+ate"*

• Dhlamdia are via%le onlinside host cells

• The set up housekeepin$

in vacuoles ithin the celle.$., a macropha$e in the

pla9ue4

•

The produce a $lucosaminecontainin$sulphated polsaccharide that is nearlindistin$uisha%le &rom heparan sul&ate

• The have a uni9ue set o& en+mes &or this: S.O. 6asmussenHathrop et al, Dell @icro%iol. 2000 pr, 224, 13IJJ

# i l ' t d t /l h i 6


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#pecial ssue 'e0oted to /l5heimer6sand n+ection:* 7ey %oints

•

!atho$ens can produce pro$ressive chronic diseaseslike l+heimer;s, asthma, and heart disease

• l+heimer himsel& proposed involvement o& in&ectivea$ents in l+heimerEs 100 ears a$o

• !atho$ens stimulate in*ammation

• !atho$ens evade host de&enses and esta%lish chroniclatent in&ections

• !ersistent superoLide, nitric oLide and peroLnitrite6


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/myloid %la8ue #tructure*

• @icro$lia and amloid pla9ueaccumulate side%side in acentral re$ion surrounded %astroctes

• @icro$lia har%or dormant%acteria

• Should the %acteria leave,the ill encounter the

pla9ue, hich ill kill them• The astroctes $uard the

$ates and shield the neurons&rom the dama$in$ pla9ue : @icrophoto$raph &rom

Scha% et al., Oournal o&

l+heimer;s 5isease 13 3B

Dhlamdia in pla9uere$ion produceheparan sul&ateQ


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#epsis and the9asculature*

(mmune cellsstick to all o&

venule and%lock *o

Small %loodclots &orm in

capillaries and%lock *o

. Tr+eciak et al., cad mer$ @ed. 2008 @a U 14) 3BBJ

(mpaired a%ilit tomodulate %lood

*o


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(4ect o+ deno0o statin treatment onpatients with sepsis plus pneumonia*

Haurent !apa+ian et al., O@,


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Hypothesis

-lood *o needs to nearl shut dondurin$ sepsisU or$ans need to shut donU

the entire %od &ocuses on harvestin$heparan sul&ate &rom the invasivemicro%es to recover %lood sta%ilit.


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)ecapitulation

• (n&ection is a conse9uence o& impaired suppl o&sul&ate to the %arriers

• Heak $ut sndrome allos %acteria to personalldeliver nutrients to the %od

• drenalin encoura$es %acterial $roth to helpsuppl nutrients under stressX4

• therosclerosis is associated ith in&ective a$ents,%ut anti%iotics make thin$s orse

•

Dhlamdia pneumoniae can produce heparan sul&ateusin$ a uni9ue set o& en+mes – 5o the help us out in pneumonia, heart disease and

l+heimerEsX


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(n*uen+a


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n2uen5a


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lu 9accine ncreases )is$ toOther )espiratory n+ections*

:-O Dolin$ et al., D(5 2012)J, 1I

•

5ou%le%lind randomi+edtrial conducted in Fon$ on$

• 11 children a$ed >1 ears –

6eceived 2008200B seasonal trivalentin*uen+a inactivated vaccineT(74 or place%o

– @onitored over &olloin$ B months

• T(7 recipients did not have asi$niKcant reduction in risk to *u

• T(7 recipients had a 44-old

increased risk to nonin*uen+a


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#upplement and 'ietary%rotection +rom n2uen5a*

• Nacetlcsteine

• 'reen teacatechines4

:S. 5e "lora et al., ur 6espir O 10 I4) 131J1.

M l / h d % i


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Muscle /ches and %ainswith lu*

?!atients ith an in*uen+alike illnessshould %e o%served &or si$ns andsmptoms o& rha%domolsis and

mo$lo%inuria durin$ the course o& theirillnessA

.s the ir%s leaching s%latero" the "%scles'

:6 @ino et al., nn (ntern @ed. 1BIJU8034)3B


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'oes n2uen5a 9irusTransport #ul+ate

• (n*uen+a virus – (n&ects muscle cells and causes muscle astin$:

– (ncorporates sul&ated mucopolsaccharidessnthesi+ed % the host cell into its on plasma

mem%rane:: – (nhi%its mucopolsaccharide incorporation into the

host cellEs mem%rane.::

.s iral inection an opport%nity to steal s%latero" "%scle cells and delier it to the lood'

: F essler et al., O@ 1B80 2J34, J>1J>2.::Nakamura and Dompans, 7irolo$ IB24, 1BII, 3813

Thi T M


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s This True MoreGenerally*

:-ernhard @uschlien, (n*ammations and Their Therap %@eans o& (so ath

copolsaccharides la%elled ith radioactive sul&ur to measure $roth

(n&ected animals

@ore sul&ur shoed up inmultiple tissues &olloin$in&ection


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&holine sul+ate""*

• !roduced % plants, lichens, al$ae,&un$i, and several %acterial species

• Lperiment demonstrated that it had

superior capa%ilities to inhi%it amloid&ormation in pancreatic %eta cells – mloid in %eta cells is

akin to amloid %eta in

l+heimerYs disease andplas a maMor role in tpe((

dia%etes

:@. Fa$ihara et al., "-S


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Tami*u and deLtran sul&ate are dru$s to suppress*u virus replication that are imitations o&

products produced % $ut %acteria

u s a t reat


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:http)//articles.mercola.com/sites/articles/archive/2012/02/0Irecommendedtami*uhas*aedresults.as

u s a t reat and Tami2u is the

answer*Side efects include) – Donvulsions, delirium and delusions

–

ller$ic reactions includin$ anaphlaLis – Fepatitis and elevated liver en+mes

– Nausea, diarrhea

– Ni$htmares

– Feadache

– Skin rash

>euraminic /cid and


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>euraminic /cid andTami2u

• Neuraminic cid) -asic unitin sialic acids

in human''s

• -roken don % ne%ra"inidase produced % *u virus

• $a"i/% inactivates neuraminidase –

This prevents viral entr into cell – Shikimate is a precursor to active in$redient in Tami*u

– Shikimate is produced % $ut %acteria


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nhibition o+ >euraminidase by'e?tran #ul+ate*

• Ne$ativel char$ed, sul&atedpolsaccharide – Snthesi+ed &rom sucrose % lacticacid

%acteria – Suppresses replication o& in*uen+a

virus strain

– (nduces viral a$$re$ation at cell sur&ace

– (nhi%its neuraminidase activit likeldue to its ne$ative char$e4

– sed as dru$ to treat *u

:F =amada et al., ntiviral 6es. 2012 5ecUB>34)3JJ


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nhibition o+ >euraminidase by'e?tran #ul+ate*

• Ne$ativel char$ed, sul&atedpolsaccharide – Snthesi+ed &rom sucrose % lacticacid

%acteria – Suppresses replication o& in*uen+a

virus strain

– (nduces viral a$$re$ation at cell sur&ace

– (nhi%its neuraminidase activit likeldue to its ne$ative char$e4

– sed as dru$ to treat *u

:F =amada et al., ntiviral 6es. 2012 5ecUB>34)3JJ

%acterium that inter&eres ith *u virus

can transport the deLtran sul&ate todistant places.

5eLtran sul&ate as a dru$ is a ?trickA.


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'e?tran #ul+ate


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-7 on 'e?tran

The antithrom%otic efect o&deLtran is mediated throu$h its%indin$ o& red %lood cells,platelets, and the endothelial cellsin the vascular all, increasin$their electronegatiity and thusreducin$ red %lood cell aggregation and platelet adhesieness.

#id (4 + ' # l+


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#ide (4ects +rom 'e?tran #ul+ateTreatment

• naphlaLis itch rash, throatsellin$, and lo %lood pressure4

• Lcess *uid in %lood

• !ulmonar edema

• Dere%ral edema

• !latelet ds&unction

The molecule %itsel& can;tmultipl

hereas%acteria thatproduce it canQQ

%hase Trial: Hepatitis &


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%hase Trial: Hepatitis &'ru1*

• Trial halted earl due to B hospitali+ations and1 death – 5ru$ orks % thartin$ viral replication machiner

– 5ru$ is toLic to heart and kidne

• Side efects o& hepatitis D treatments, more$enerall, include anemia, cardiacarrhthmias, severe depression, and *ulikesmptoms

• Dholesterol sul&ate is a natural inhi%itor o&Fepatitis D::

)//.thescientist.com/Xarticles.vie/articleNo/322/title/DlinicalTrial@is&o

uruta et al., O n+me (nhi% @ed Dhem. 2013 "e% 2. Vpu% ahead o& print


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)ecapitulation

• -etter to prevent *u than to treat it

• -etter to prevent *u throu$h nutrition thanthrou$h vaccines

• "lu is associated ith achin$ muscles) is thevirus &orcin$ muscles to $ive up their sul&ateX

• Treatin$ *u can lead to severe ?side efectsA – re these the conse9uence o& the virus %ein$

a%orted earl %e&ore it can &ollo throu$h on itspromise to deliver sul&ate to the %lood streamX

• ( suspect man other viruses e.$., hepatitis D4provide muchneeded sul&ate to the %od


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Natural 6esistance and nti%iotics

Multiple /ntibiotic


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Multiple /ntibiotic)esistance

• nti%iotic resistance is a serious and$roin$ threat in modern times

•


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,', %rotects +rom M)#/*

eterson et al., Dell Fost @icro%e J>4) >>, 2008

•

@ethicillinresistant Staphlococcusaureus @6S4 has %ecome amaMor pro%lem inhospitals orldide

• po- in H5H limits invasion % %indin$to and neutrali+in$ a ke

en+me responsi%le &orpromotin$ invasion throu$h

the skin

• Skin penetration and %acterial densit eresi$niKcantl $reater in po-deKcient mice.


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Th M)#/ ( id i *


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The M)#/ (pidemic*

:@. -erens and . rmstron$

Fo our hospitals unleashed a @6S epidemic Seattle Times 111>, 2008


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M)#/ in &hildren On The )ise*

• The in&ections overhelmin$l resulted inhospitali+ation B1C4U >C ere &atal.

• @ost o& the afected kids >8C4 had anotherunderlin$ medical condition, most commonlprematurit 1BC4 or a skin condition such asec+ema or a%scesses 18C4.

• -lack children also had a disproportionate

share, accountin$ &or BC o& the cases, ithan incidence o& >.I versus 1.> per 100,000amon$ other children.

:Drstal !hend , @edpa$e Toda Sept. 23, 201

&lostridium 'i@cile and 7lebsiella


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%neumoniae /re &omin1*

:.Mon%arron.or$/topic/clostridiumdiRcileandkle%siellapneumoniaearec

• To super %u$s resistant to nearl all anti%iotics

• -reakouts in hospitals are dire threats• Suscepti%ilit

– Weakened immune sstem

– 5isrupted $ut %acteria

•

Dlostridium diRcile D. dif 4 – Spores are nearl indestructi%le

• Ne kid on the %lock) le%siella pneumonia superstrain –

6esistant to ever sin$le anti%iotic in the medical arsenal. – nclosed % a polysaccharide capsule that protects &rom

anti%iotics

– (nitiall *ulike smptoms

• hi$h &ever, chills, cou$h

• copious amounts o& viscous and %lood mucous in the

uoro8u nones: o? c/ tibi ti "*


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8/ntibiotics"*

• mon$ the most commonl prescri%ed anti%iotics in the

S – (nhi%it %acterial 5N snthesis

– "luoride increases penetration into ---

• Smptoms include) – Nervous sstem smptoms tin$lin$, num%ness, anLiet,

memor loss, pschosis ..4

– @usculoskeletal smptoms tendonitis, eakness, Mointsellin$ ...4

– Sensor smptoms tinnitis, altered vision, ...4

–Dardiovascular smptoms tachcardia, chest pain,palpitations ...4

– Skin reactions rashes, hair loss, seatin$ ...4

– 'astrointestinal smptoms nausea, vomitin$, diarrhea...4

icles.mercola.com/sites/articles/archive/2013/0B/2/*uoro9uinoloneanti%iotics.


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)ecapitulation

• @ultiple anti%iotic resistance is a$roin$ pro%lem – Dould it %e due to insuRcient cholesterol

and insuRcient sul&ateX• "i$htin$ disease ith anti%iotics (s a

losin$ proposition –

5ru$ resistant micro%es lead to evermore toLic anti%iotics

– Side efects o& the anti%iotics can kill ou

#ummary


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#ummary•

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3 Gut Bacteria