Ass. D-r Sowa Bojaxieva Univerzitetska Klinika za detski bolesti Oddel za gastroenterohepatologija Definicija: “Probiotici se `ivi mikroorganizmi koi, dadeni vo soodvetni koli~ini imaat pozitiven efekt vrz zdravjeto na doma]inot”. FAO (Food and Agriculture Organization of the UN) and WHO 2002 Working Group Report on Drafting Guidelines for the Evaluation of Probuitics in food.London, Ontario, Canada 2002. Pozitiven efekt na intestinalnata motorna funkcija Modulacija na inflamatornata odbrana Podobruvawe na funkcijata na mukoznata bariera Inhibirawe na rast na patogeni mikroorganizmi produciraj]i lactic, acetic i drugi organski kiselini, namaluvawe na pH Kompeticija so potencijalno patogeni bakterii za nutriensi i epitelni adhezivni mesta Aktivirawe na specifi~ni imunolo[ki mehanizmi (Bifidobacterium bifidum i Streptococcus thermofilus) Lactobacillus Bifidobacterium Lactobacillus acidophillus group-(Lactobacillus acidophilus, Lactobacillus gasseri, Lactobacillus jenseni, Lactobacillus crispatus) Lactobacillus casei, Lactobacillus paracaseti, Lactobacillus rhamnosus –Lactobacillus GG (ATC 53103) LGG Lactobacillus agilis Lactobacillus salivarius Lactobacillus plantarum Lactobacillus Pseudoplantarum Lactobacillus bucheri Lactobacillus reuteri Prebioticite se nedigestibilni dietarni suplementi, tipi~no oligosaharidi i disaharidi so pomo[en efekt na doma]inot, za selektivna stimulacija na rastot i/ili aktivnosta na limitiraniot broj na bakteriski speciesi koi se ve]e prisatni vo debeloto crevo. Diplock AT, Aggett pJ, Shwell M, et al. Scinetific concepts of functional foods in Europe;consensus document.BrJ Nutr 1999:81(1):1-27 Synbiotic = pre + probiotic Kombinacija od nutritivni suplementi koi se sostaveni od pre i probiotici Sinergizam za da se zgolemi korista na doma]inot. Fooks LJ, Gibson GR.Probiotics as modulators of the gut flora.Br.J Nutr.2002:88:S39-S49 Inflamatorna bolest na crevata Ulcerozen kolit (UK) Crohn-ova bolest (CD) Nekrotizira~ki enterokolit (NEC) Infekcija so Helicobacter pylori Colon irritabile Ulcerozen kolit Crohn- va bolest Nastanuva abnormalen imunolo[ki odgovor kon normalnite crevni bakteriski antigeni. Vo tek na imunolo[kata reakcija se aktiviraat proinflamatorni i imunomodulatorni molekuli, pri [to doa\a do naru[ena interakcija pome\u crevnata mukoza i mikroflorata Shanahan F.Inflammatory bowel disease:immunodiagnostics, immunotherapeutics, and ecotherapeutics. Gastroenterology 2001;120(3):622-35. Torres MI, Rios A.Current view of the immunopathogenesis in inflammatory bowel disease and its implication for therapy.World Gastroenterology 2008;14(13): 1972-1980 Citokini so proinflamatorna funkcija se: Interleukin 1 (IL-1), tumor nekrotizira~ki faktor alfa (TNFα), IL-6, IL-8, IL-12 Antiinflamatorna uloga imaat: IL-1 receptor antagonist (IL-1ra), IL-4, IL-10 i IL-11. MacDonald T, Path FRC, Disabatino A, Gordon J. Immunopathogenesis of Crohn’s Disease.Jour.of Parenteral and Enteral Nutriotion 2005;29:1118-125 Apathogenbacteria Bacteriocins Cross-talk between Gut bacteria and the intestinal immune system Privremena modulacija na intestinalnata bakteriska flora Inhibicija na TNFα sekrecija kaj pacientite so ulcerozen kolit. T.Mach.Clinical usefulness of probiotics in inflammatory bowel diseases Journal of Physiology and Pharmacology 2006,57, Suppl9,23-33 Bacteria Probiotics Intestinal mucosa IL1, IL6 TNF MO IL12 IL2, IFN↑ Apoptosis Th1 ↑ Chemokine Adhesions molecules TGFß IL10 Th2 ↓ BV Benefit - remisija na blaga i umerena forma na UK T.Mach.Clinical usefulness of probiotics in inflammatory bowel diseases Journal of Physiology and Pharmacology 2006,57, Suppl9,23-33 Terapija (6 nedeli) so ne patogeni vrsti na E. coli Nissle 1917 i probiotik preparat VSL#3 administriran vo mnogu golemi dozi (3600 bilioni bakterii/den) remisija kaj 77% od 32 pacienti so ulcerozen kolit. Bibiloni R, Fedorak RN, Tannack GW, et al. VSL#3 probiotic-mixture induces remission in patients with active ulcerative colitis. Am J Gastroenterol 2005; 100: 1539-1546. Vo studiite ne e doka`an benefit od tretmanot so LGG vo lekuvaweto na deca so CD. Michael Schultz*1, Antje Timmer1, Hans H Herfarth1 et al. Lactobacillus GG in inducing and maintaining remission of Crohn's disease BMC Gastroenterology 2004, 4:5 Bousvaros A, Guandalini S, Baldassano RN,et al. A randomized, double-blind trial of Lactobacillus GG versus placebo in addition to standard maintenance therapy for children with Crohn’s disease. Inflamm Bowel Dis. 2005;11(9):833– 839 Lekuvawe so probiotici kaj vozrasni so S boulardii, LGG, i E coli Nissle 1917 sé u[te nema vetuva~ki rezultati Schultz M, Timmer A, Herfarth HH, Sartor RB, Vanderhoof JA, Rath HC. Lactobacillus GG in inducing and maintaining remission of Crohn’s disease. BMC Gastroenterol. 2004;4:5 Plein K, Hotz J. Therapeutic effects of Saccharomyces boulardii on mild residual symptoms in a stable phase of Crohn’s disease with special respect to chronic diarrhea: a pilot study. Z Gastroenterol. 1993;31(2):129 –134 Malchow HA. Crohn’s disease and Escherichia coli: a new approach in therapy to maintain remission of colonic Crohn’s disease? J Clin Gastroenterol. 1997;25(4):653– 658 Prantera C, Scribano ML, Falasco G, Andreoli A, Luzi C. Ineffectiveness of probiotics in preventing recurrence after curative resection for Crohn’s disease: a randomised controlled trial with Lactobacillus GG. Gut. 2002;51(3):405– 409 Cochrane studii - sé u[te ne e doka`an benefit i remisija posle administrirawe na probiotici kaj vozrasni so Crohn-ova bolest Rolfe VE, Fortun PJ, Hawkey CJ, Bath-Hextall F. Probiotics for maintenance of remission in Crohn’s disease. Cochrane Database Syst Rev. 2006;(4):CD004826 Lactibiane Tolerance - antiinflamatorna uloga, stimuliraj]i produkcija na IL -10 kaj in vivo predizvikan kolitis na eksperimentalen model (`ivotno), < simptomite kaj 50% pacienti so IBD (p<0,01) ? Clinical Nutrition Decembar (2006)25,994-1003 Sophie Drouault-Holowacz, Benoit Foligne, Veronique Dennin Denise Goudercourt, Kathleen Terpend, Andre Burckel, Bruno Pot PileJe, 37 Quai de Grenella, 75738 Paris Cedex 15, France Bacteriologie des ecosystemes, Institut Pasteur Lille 1, rue du professeur Calmette, BP245, 59019 Lille Cedex, France Pozitivniot efekt - vo terapija na ulcerozniot kolit so probiotici. Generalna preporaka za nivna primena kaj decata so UK nema. Probioticite ne se prepora~uvaat vo lekuvawe na Crohn- ova bolest vo detskata vozrast. ESPGHAN American Academy of Pediatrics.Clinical ReportProbiotics and Prebiotics in Pediatrics.Dan W. Thomas, Frank R. Greer and committee on nutrition; section on Gastroenterology, Hepatology,and Nutrition. Pediatrics published online Nov 29, 2010;Downloaded from www.pediatrics.org by on March 1, 2011 Definicija: abdominalna intestinalna reakcija i razvoj na abnormalen inflamatoren odgovor na hrana vodej]i do intestinalna nekroza. Prematurni - 7-10 dena od hranewe Zreli novorodeni 1-4 dena Svetski mortalitet 25% Asocijacija so NEC: infekcii, srcevi anomalii, naru[ena intestinalna cirkulacija, gastro[iza, nozokomijalnite sepsi . Nezrelost na imuniot sistem Nerazvienost na receptorite Nerazvienost na sekretornite mehanizmi Nedostok na enzimi Motilitetot na crevoto Gestaciska starost Na~in na poroduvawe Maj~ina flora Flora na okolinata Vid na ishrana Nedonoseno pred 37 gest.nedela - nezrelost Motilitetot na crevata e vo korelacija so gestaciskata starost Nezrelite motorni funkcii -razvoj na abnormalna flora. Nedostatok na sekretorna antitela Kolonizacija na patogeni mikroorganizmi Bakteriska translokacija Pickard L.M. Brommer AR. Cordon J.N. McDonald TT. Immune responses.BestPractResClinGastroenterol.2004;18:271-85 Prevencija na NEC Pozitiven efekt na intestinalnata motorna funkcija modulacija na inflamatornata odbrana podobruvawe na funkcijata na mukoznata bariera. L. sporogenes- administriran vo doza od 350 000 000 c.f.u. so maj~ino mleko ili formulanema efekt vo namaluvawe na incidencata i mortalitetot na NEC kaj prematurni so mnogu mala rodilna te`ina <33 g.n.<1500gr. Efekt: ja namaluva intolerancijata na hrana 44.5% (n: 49) vs 63.1% (n: 70), o~ekuvano p=0.006. Sari FN, Dizdar EA, Oguz S, Erdeve O, Uras N, Dilmen U. Oral probiotics: Lactobacillus sporogenes for prevention of necrotizing enterocolitis in very lowbirth weight infants: a randomized, controlled trial.Eur J Clin Nutr. 2011 Jan 19. [Epub ahead of print] Lactobacillus GG Probiotic Bacteria in Dietetic Products for Infants:A Commentary by the ESPGHAN Committee on Nutrition Journal of Pediatric Gastroenterology and Nutrition 38:365–374 2004 Lippincott Williams &Wilkins, Philadelphia Lactobacillus GG - nema efekt Dani C., Biadaioli R., Bertini G, et al. Probiotics feeding in prevention of urinary tract infection, bacterial sepsis and necrotizing enterocolitis in preterm infants. A prospective double-blind study.Biol.Neonate 2002, 82:103-108 Lactobacillus acidophilus i Bifidobacterium Benefit - kombinacija na probiotici vneseni oralno so maj~ino mleko mo`e da gi za[titat novorodenite so mnogu mala telesna te`ina od `ivoto-zagrozuva~ki sostojbi. Lin HC, Su BH, Chen AC. Et all.Oral probiotics reduce the incidence and severity of nwceotising enterocolites in very low wiight infants.Pediatric 2005;115:1-4 NEC ESPGHAN Generalna preporaka za rutinska upotreba na probiotici kaj prematurni novorodeni za prevencija na NEC sé u[te ne postoi. Benefit - dozi so LGG (6x10 10 cfu) vo tek na 2 nedeli gi namaluva negativnite gastrointestinalni simptomi (gadewe, dijarea) vo tek na tripla terapija za Helicobacter pylori infekcija. Doka`ana e podobra tolerancija, no ne i eradikacija na samiot Helicobacter pylori. Dvojno slepa, placebo-kontrolirana studija. Armuzzi A, Cremonini F, Bartolozzi F, Canducci F, Candelli m, and al. The effect of oral administration of Lactobacillus GG on antibiotic-associated gastrointestinal side-effects during Helicobacter pylory eradication therapy.Aliment Pharmacol ther.2001;15:163-9 Benefit -eradikacija na H.pylori kaj 91% od decata, v.s. 78% samo so triplterapija. Sheu BS, WU JJ Lo CY, et al.Impact of supplementation with Lactobacillus and Bifidobacterium-containing yogurt on triple therapy for Helicobacter pylory eradication.Aiment pharmcol Ther 2002:16:1669-75 Pre i probioticite go namalile vremeto na lekuvawe kaj deca od 1-6 godini i signifikantno se zgolemil brojot na laktobacilite vo feces. Schrezenmeirj, Heller K, mccue m, Liamas C, Lam W, burow H, KindingRohracker M, Fischer W, Sengespeik HC, Comer GM, Alarcon P.Benefit of oral supplementation with and without synbiotics in young children with acute bacterial infections.ClinPediat (Phila).2004;43(3):239-49 Edno od naj~estite funkcionalni gastrointestinalni zaboluvawa so prevalenca od 3-15% vo generalnata populacija. Povolen efekt vo tretmanot na Colon irritabile so probiotici. Andresen V., Baumgart D. Role of probiotics in the treatment of irritable Bowel Syndrome:potential mechanisms and current clinical evidence Inter.J of Probiotics and Prebiotics.2006;(1):11-18. Viola Andresen and Daniel C. Baumgart Role of probiotics in the treatnebt of irritable bowel syndrome:potential mechanisms and current clinical evidence.International Journal of Probiotics and Prebiotics Vol.1,pp.11-18,2006 Potrebni se idni studii za sigurna i efikasna suplementacija na probioticite vo detskata vozrast. Evropskata asocijacija za pedijatriska gastroenterohepatologija (ESPGHAN) ne prepora~uva rutinska primena na probiotici vo detskata vozrast. Benefit od probioticite Definirawe na minimalni i optimalni dozi vo detskata vozrast Bakteriski fragmenti i bakterii so genetski in`enering, kako alternativa na probioticite so cel da se podobrat sakanite korisni efekti. Vo idnina: nivna klini~ka primena vo pedijatrijata. Ilya Ilyich Mechnikov 1845-1916 "Eat foods containing these bacteria L plantarum, L rhamnosus, L paracasei, L acidophilus, and L salivarius to heal your body and add years to your life "
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