Treatment of Ulcerative Colitis Using Fecal Bacteriotherapy “Thomas J, Borody, MD, FRACP, FACG, FACP, Eloise F. Warten, BSeM, Sharyn Leis, RN, Rosa Surace, and Ori Ashman, MA. Abstract Background: Altuph holy of oaicwarate cols {Uc remain ory tern eel lon ape Py pra le Spe cne stain ee ‘SaaS os has bon care y Tne fs 0 Ws toon Tint slo. Ts appre malo Be ap (SR tothe eeu of UC on te fae of een va {menace Gono stueve the Sinaloa sd fog ease aftonan probit ifens OI § Sete bes wih UC Case Reports Sx patents (ten and men en 355 yen) UE fr ls tan ea ners ee 1 Apa ha lee ne mera ype an UC ‘nor wore hey an nto here exesvel seen or fare and ace page, Pons mere pyar with {isout an al peter een nage Fel suspensions ‘tow ministered eeton cama in 10 antes ot ea {aoe ae th os oped dy or’ ay By Toe pos FiPrsome spon of OC ha npr, Complae reveal of Syst aleve al pn aa pac Zlncalcolipc or haloic een of UC nay et “Conlon Coss nin 9f Sor na sestia oa SoTexen UC islet patent These tector sp pet cnet sea el om ores spe sb ‘eid acer puhopen cane UC io Were cen, path lant bowel Tregettann a tant urine) sone snot novel concep, ving Boe practiced periodically for more tan 40 yeas." Bacteriothrpy ti Tring human fees bas been reported 10 achieve success ner antiboics have fied While the Best known applic Cation of Bactrotherapy inthe weatent of unresponsive ‘Cosridm difitesuarbea and pseudomembranous cle {is significant ciniea improvements have als Ben potted in other GI conditons incloding constipation, Iritable bowel syndrome (IBS), and inflammatory bowel disease (BD).™= eer ce rete Dene ye a [en oreemns rene Or a | Bay 2 Atiouh the pathogenesis of ulcerative colli (UC) is ‘nclear, one hypobenisatibutes the etlogy and pers tence ofthe inflammatory proces othe testinal oa Peps a viral bacterial hema "rigger invokes an ‘overly ageresive ost mune response tat perpetuated bythe resident lor lng fer hei afeton bas re sete" Loss of tolerance to the nocmalIuinal con tens caused by abaormalies in mucosal permeability or a lack of regulatory clldmeiators als hogtogive is to chro nflammaton i genetical suscep indivi ts" Given the complex compostion ofthe nesta ‘rats ao faible atthe hone rewtet nara ti ssid with UC the rest fa persistent infection with specie, uta yt unidentified pathogen? “Te ue furan fecal batrotherapy may have a role in the testmem of UC since sas consistently demon Stated easy aginst Cie colts Farbermore, Benge and Beinkman" reported prolonged remission of LUC inthe absence of C. dif afte the administration of ‘single focal enema, With thin ming, we eed ou fecal ucteritherapy in 6 patents sueig longstanding iio- phic UC. Because human feces maybe regarded the ‘imate probiotic mixture, the proved el was ees ‘Shuman probiotic ifsion (HPD The esata long-term follow-up are compile here asa Sees of 6 case repos MATERIALS AND METHODS, Fea acta wpm 6 pai ale 3 fe gel 38) Hea no Pg. et ‘Shun Surssene swe by pens pr to reccvng feamove All pues had eabed UC or ore tan 8 Jers ‘rh tnenammato set inl ago lowe py nd sly Sot cure and mecopy tert fo cack fata wae mg for commen detecte cet popes (Going © ft ond eon. Al ten hc fated un tum crac std UC herpes mae ata dase tell on wal oman pees msc r desea Tate. Peis meieaas [Reap ined mento hphoe tread ‘atmo agent Ainge dap were pry eleven {Soncing te sce of sqm ia 8 pent he de inne dune rrted ce When hese medics te ick dicomiacd ured symone ec. Tee pate for espero id het fog asteront ramet of Ue Cote ‘TABLE 1, Paton presatment chaactnates snd medeatins sown = a Darton of deese yeas) 8 2 Fasmos Reem Soon Sag. Pez moms ce mee (Dose doaten porto He) Sto Cmts) ones) a Foesogs Faompy — Passamad b2s-50 9 Acatomge Acitsmae Academe Acvesimga tents WeSrsea cans S208 Ba mo P20 nomi Pome Pomp Pas Pema Aoatdmgs Gags Acad Ata git heweoe Mectoree Mes ME~2o8 (Eee treme rome) la (Sins) ’ rhe 6, arian CF, daerne: CP, cdenepspate, Coc, erbu P,hanan pb fon «cen veces i nba Eerie WP meray Oo inward abou poe or erent Py were suid ah a vate plied ae "ia ig te wef Neto for trea ab {Shuey ise writen weed fred case ‘vac eaten ev lef loco EBC), qi ent i Ea Cae Pace CR. try. Mos prance wee revel mts the HP 1s apn set yen nue [23am prmetas ere Irere pana 313. and 3 yes eps Al pues Selection of Donaes bons wer ost naomi sue dno or HPL boas met sete fees ale th ermal bowel {ce a hr aims, hving ken to setts fer at Ibo aks They wee come econ FBC ra LT ee inna gest leg we {nl sp Dor fel specimens were em Sle ‘mc for comms pagar i Sloat Shige ad ‘Compton sp roma hyp Yeria sp. WOrio. remotes Vir celery, Cada leant enero ecorag Fos 17,2 Clara if un su ‘Momscoy wat neve fr yr poner aed 3) ‘nn vt eng moc tte. Car an ig, Copsporidn sp. Dioocba frags, Blasecrtis: ‘mints ears ite, ems dtp we Administration of Fecal Suspension resin of lst sass 30 emt 40) ‘Reba a arpcin 190 mp fo 710 ay) flowed y 8 ‘Tene os ovge ih 3 Lo pobetyene pica bet bn es 0-20) wi it in 201 30 a ea ‘epraoPatens wee econo oon th enema os. Ina pst ett 4 Tac pcan a epee aly forays hp dw ab sn eng sma Pliesion sheng haters All asm thers {eww imey pose HP resent patra Ho Svea pten ane 38 CASE REPORTS, Patient 1 1 26yearil anpeet with ye ty of UC. He adept urd rs 1? [besand wept nso ekg oner eam ad resin bo tre ih peonone 28 mg taopan 326 codeine pho“ sit 30 mg a ily pore a ap {BS fey head ra Sir chee lyme pte Sita nels al tse ie Si ie Re fice eso ro on ed simatic faye, we pt ne seca we Shale Pas {Pbiuaingt wempepine (COT prenmel vo tne bes Pr EARS ATH mus cng ce Tm mec HAL ak ype ne rly ct ite pane nen pene Seas ts toct ocala rr Tet ettom ences syne ly sorte wet ec He ee eatin tao Foss pM reed ter Tue ann, iad in py siting he ppm iets progeny retired ema ckimed may ee etc wpa roe Oran mes ca Soe ae fm ow Se hry a Sueur idee bite Ue oe heogrgy Lope nel sete ere me Patient 2 “Tis yet won bt 20 ea istry of cri UC nly Sepnsed emer Se ha prevent ed ‘tpn posi lyn ter enc in aa co inca tte lly Taman 00 revi Chuts'penne ss mgs mavonzte 200g oper Shang il ns sendy wl ainners Wh Toning dss (gh nes reached ve th eae buhay) On pean oe compel of cl led Mie"and dines Gok motions per dy) Sih rman ‘Shainin sal cumg, gene. neice She foveal ea refuel of tae, ond ened ‘Shae omar tcp cng he Hoa manila ‘fap of Benet and Bran Tone uP ao i gmploma Teme estmscoy r- ‘call pay nem thnges nave of nse 1D Hip mascot wt CC ftp at PL ‘oe enemas wee nied eer Score a Te TER gin fo am acta sd ae done Slr fou the oly como ofc af tine, wos ceed Tm naw ys syns ingoved mst IR'Tonen ys HP ona and hate sboed no cant geal hed chose aati. Te pate a nity sr ts fst Sresng oo 2 ot sols et fy wi ao asmined yop At flowy soesutston SO'jea ge she sol he agmpoma Twee as psy the was mcr cmscopi ein fr ‘nc ct Hoogy mas ape for bah SNe and co Patient 3 "A? i ae apne rected witha Se sty of sete UC ne ig 01 eo th ‘eas ot ger esos wer parla (esa on sna ena sate madatons ling ‘ghioe sev 2 pds mesmane #6 olson 30 48 ppnow sci il comes of abt 30) mg laos (900 teeth, saturn (180 mpi) and ctl 00 ma) Dod ‘levy ea tise eb oe Pay ‘iter sc aco eve Insp es nee hen ‘sul oes he ay poe ape elo 50g ‘Cejucton wa er dus hot spam eer Coke Sczopy is tne cond poe te coli wa ont irc misting pte sf acne soo IRD Boo oe ‘evel mid popes ad ote “htc ome symp th preston. seme erie ache ae Hn ‘rel esp eps of ont net te in comment nana ee eh [igs nd es, reine ws ded ip ‘thes me parol Oe mom cr Ha {edly with inal lod an ete Heh ‘Sopra seer heh On ea pox the pate Was Fm ey es Mann or Ars yea inte poo, be roads ca sl aan ‘Sop on wth pte fe da rem shown rane cca sg a ip cee out Patiot 6 1 26ers woman psn witha Hear tory of UC incbing des wah sedi 3S tons per ay ‘Sopig: n,n, omaton of lee tine ad Aine Despite ips, siete mpm’ record every fe Inet, esl ing sss, nent fsa Sabi colomssycaly wit ace clei nian Shans, sympoms nce pty como over seve ona {pedis 0 me suze Saag 18 matt (thine whch amcopenta develops) nd br tang 0 RET HP, done wa eo 0 2D malt ate of meek HPL mt ug flrs oat he pe erin fer cocuve days Mepis an Seb. Inmate inpronemens ice reduced ceding. [Soy amen and ving whl sini carping peed eVect heen expen ep of edig! wosks tL on a tl ithe of pen wos el at REE te mon fllowing HPL he ptt wan wel i n> Fa rN 2 pus fo a ead hl 0 oe CC ‘ely depen esr am aed eine. {olomoscopicy, and histologically siease-ie witht Patient § syed woman pee wh |S year story of aa wil She nse or ui pedis ¥0 mg, eaopeine 200 mp. meson=te praca bt sy ped cn wi of ts FIGURE 1. Patents, porto HP: Descending enon wih Inenee UC vst on clonosany FIGURE 2. Paton 51 year p0stHPI: Normal mucosa wth ome searing. DISCUSSION Atough tes ae case repos several observations eat be made Al patients id docuncsted sdopathic UC with tn alwenos of detectable festive agen Compete ves F UC was scived i all 6 patients following the infusion ff human fecal flora. All patents ceased ant-ilanatry therapy win 6 weeks nd di ot equ farther weament ting the extend follow-up pevod. Aer 1 13 yeas patients remained symplomati with aly eolono ‘Copic appearnce nd noc istlogy, Though there Tite dou that UC can o int lnc remisston, chronic UC as ot bcm noo to spontancausyresave bath ao oscopically and histologically without elapse for upto 13 as observed re To our Knowledge, thee cases ocament for the fist tine the Tol disappearance of ‘tonic UC witout the need for maintenance Uestnen ‘This san unprecedented finding tht deans explanation hoe fuer reser ‘Ou cases ifr from the remissions comonly see in linia patos. Remission in UC is a erm dessin la tian lin mprovereat ten measured by an aetviy index. Tete Is samen no defisition of remission that Aemunds colrascopc and bistolgie noma wih no« currence after a proonged period without mediation, Per hap nthe fut f sch heap ean achieve plonged thence of UC without mtintenance digs, the esl should te oomsidered a “cure Before posusting the therapeutic mechanism of fecal tuceithsrpy Ht shoul fist be noted thatthe ctlogy of UC remuine the topic of mich conjecture. The pathogenesis fof UC may involve the presence ofa as yet undesrbed Pathogen Speci tsi infctions eased by Salo rll, shigella, ersini, Campstobatr,Eatamoeha hist Iie and Diontmocba fragilis olen resemble thase of UC?+ similis, colonoseopic and histlogi appear tances ofthe howl in idiopathic UC ca at Hes mie ‘hose peseat inact infections ‘Since UC is characterized by persistent ilammtion, it iscoecivable tat th disease proves i driven b a eroie infect aided perhaps y the aoe of spor luminal Stacrbes constiuing the colonization resistance of the owe I the ability of the orma fra to ress colon “ato by pathogene is redace, by previo antboic wse for example, the numbers of protestive anaerobes in the towel, suchas Barteroides spp. detne. This woul pert the impentation of ther palhgenic anaerobes or Sper fearing baceia and a fm of recent, croc cols ‘woul ene "Te crit of UC could he de othe implantation of sores inthe micosl surface, analogous 19 Csr Unite infection. Aoibos may lp wasn But ae nicely toe caative because the sores are not era fate.” Fecal baceiatbenpy however capable of euing ifie infection and the sect caliis® Since a Similar phenomenon as ben observed here i Seems tibet sigest that UC may also be sustained by 2 pers tent gastrointestinal infection with some undiagnosed trcteium,pemape invasive or spore bearing. whichis i= {ually imposible to eradicate with coment ambit “Though no pathogen bas Been Hci as the definitive cause of UC, some differences between pormal and UC fora base been reported. Patents with UC are know 10 hve aboormalyelvaed numbers of fell) anaero- bie bacteria” Adhesive Escherichia col? and. move freely invasive Fusobacterium vara have been oni ted as posible UC patogens ‘suing then ha UC ts proportion of pe tins isthe rest of chronic infestion wah aspect oye, eal bateroterapy might ai inthe reversal of the cond hy rsntodsing species that ae capable of fmgonizing the putative caves agent Tas has teen Known to ovr by competitive exclusion whereby the in ‘oming tcrobes compete with ce pathogen fer ete me {ens o eithla adhesion sites" or byte production of canta re airy t the growth o adhesion of the pathogen Fealfatetoterapy may ae: rg the re-establishment of essential anaerobes, esoring mba nce of composition and metbelis.”"? “The bradspecrn antimicrobial ivi of fv Nora is also thowgh to protest the bowel fom invasive path sons A single sty has examined the amir tion ‘ofthe complete feel flora hie is invidul compe nents, sch 36 Group D steptococc, and cera trai of Escherichia elt. Lacobacla and. Bfbactri sp. ave been show fo sopartly xe profound inhi lets asia range of pahogeni bacteria. acai {lift ada. ome poral flora componen’s Pradcebacteioin that int the prow of pathogens" Ts been proposed tht aboomalites i tics pe meaty may lio give net UC by lowing nla tory bacterial compres Yo access the nes immune System:®=" Probonisreinrded to the bowel By foc acteroteriy may’ eo enanceiesinal Bari fae thn and dowreulte the production of po-inarnatry token Pics have alo ben sept 0 aller the mca mane stat hough bats “priming” of fucssociatd Typhoid tse and by modelling gut svocsodIymphoid a epithelial ese espnse The tii of probiacs to impose the activity of intestinal tracrphages and natural ile ells, ct the praliferaton tf lymphrsyes, and inrease IgA potion, could also be factor contin othe siccexs of bacteroheapy.* Se Jeced sais of probit are ls ble o mois macs fn systemic immune Fanction, ica simulating m0 ol production of IL-0 and spxemic Th2 esposes, Icading tothe reajastncat of the T- 177-2 mucosa al nce" Foal bacteviotberapy may implant and propaga rca species tht alr te imine Blanc watin te tmocona esting inthe reversal of UC “There exists only previously published case of UC where symptoms improved feel hacteioheapy" I. {lee rom our cise n han clonoscopic o hsoogie ‘vidence of UC dsapearace was provided ate leet to the Lancet. Nevereless, combined with our ease reports, tm argument could be made to soon fre esearch ine the mechanisms of hactenoheapy io UC especialy ies necdotl reports ave clined the Dents of fea Tra intasions for other GI conditions, nach as antibiotic ‘Sct dures, constipation, and IBS, wit the dem ‘stated presence of specie elope pathogens “he ssnaton of the bypethesied patopen responsible foc ination and persistence of UC would cable future therapies to target speife causal spent Unforanatel, {dette complesity te intestinal rs, complee analy Sis ofthe compostn of fla and sonication of pattie UC pathogens renin problemate, Farhermor. complet Analgis of dopor feces was also aot possible Tor donor Spevimens using corneal cle wehagues. Homeves, ‘eccal edvancesn molecular biology should progressively ble the Keaton and quantiaton of fecal bacterialspecies in fre studies incling pathogens, via polymer- she chain reaction (PCR), and ther mlec-aci-based ‘ection methods, In combination ith randomized con- trolled tls agaist pte causal age this venue has pote to depher th pei role ofthe fuminal contents Inthe pathogenesis of UC REFERENCES. "tg ig Bn le i 9 «Eyre refed tn 7 Basie one eo «Rabo sce wus bw ome? Ne a '* spietaasea'e set ama ms oe raman of Ucerave Ci ” 7 Totland ean ‘Sone cies come an ae ee 4. i rt A, Cy PL of ret ca as ral ax eee la se of ce sx imitate msn A ian ea ena smn ee