Clinical Guide to PROBIOTIC SUPPLEMENTS AVAILABLE in CANADA: 2014 Edition 14 N 0 E 2

Clinical Guide to PROBIOTIC SUPPLEMENTS AVAILABLE IN CANADA: 2014 Edition 14 N 0 E 2 . W

Indications, Dosage Forms, and Clinical Evidence to Date R

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R Author: Dragana Skokovic-Sunjic BScPhm RPh NCMP A O T Reviewers: Dr Vivien Brown MDCM CCFP FCFP NCMP, Dr Bradley C. Johnston PhD, Iris Krawchenko BScPhm RPh, Dr John Marshall MD MSc FRCPC AGAF, Dr Tom Smiley BScPhm PharmD Medical Editor: Ivana Sunjic BSc ACRONYMS

ID Infectious diarrhea IBD-UC IBD - Ulcerative colitis - Adjunct to standard therapy AAD Antibiotic associated diarrhea - Prevention FAP Functional abdominal pain

CDAD Clostridium difficile associated diarrhea - Prevention CID Common infectious disease (children) NEW CD-PP Clostridium difficile associated diarrhea - Primary Prevention CE Childhood eczema NEW TD Traveler’s diarrhea PD Periodontal disease NEW C Constipation LDL-C Reduction of LDL and total cholesterol NEW Regurg/ Reduces regurgitation/Improves gastrointestinal motility * Preterm infants 34 weeks of gestation, formula-fed GI Mot ❄ Product requires refrigeration HP Heliobacter pylori - Adjunct to standard eradication therapy CFU Colony forming units (number of viable bacteria) IBS Irritable bowel syndrome M = million , B = billion, L. = Lactobacillus, IBD-P Inflammatory bowel disease - Pouchitis B. = Bifidobacterium INCLUSION CRITERIA

All 3 must be satisfied Note: • Commercially available in Canada as a supplement • For products containing multiple strains, evidence or probiotic-containing food must be for the specified combination and not for • Approved by Health Canada the separate probiotic strains (NPN or EN - Natural Health Product Number) – • Some products are excluded from the current edition for probiotic supplements (tablets, capsules, sachets) due to changes in strains used • Published clinical evidence for the particular • Please refer to individual publications for specifics strain present in each product/food of patient populations studied and details of clinical effect LEVEL I : center or research group / Evidence obtained from multiple time Evidence obtained from at least one properly designed randomized trial. series with or without the intervention. Dramatic results in uncon- trolled trials might also be regarded as this type of evidence. LEVEL II : Evidence obtained from well-designed controlled trials without LEVEL III : randomization / Evidence obtained from well-designed cohort or Opinions of respected authorities, based on clinical experience, case-control analytic studies, preferably from more than one descriptive studies, or reports of expert committees.

DISCLAIMER: In the case of probiotics the clinical evidence only supports certain formulations/brand names of the probiotics (including the genus, species, alphanumeric designation, number of live bacteria present, the blend of probiotic strains present, and finally the non-active ingredients present). Every attempt was made by the author and reviewers to include the published clinical data on every probiotic formulation available. No bias is intended toward any one formulation.This chart is reflective of published evidence available up to date. It does not represent endorsement of any specific product. It has been produced as a tool to assist healthcare professionals in providing evidence-based recommendations to their patients. Please forward any questions or concerns to author Dragana Skokovic-Sunjic at [email protected]. 2014 Version, valid until Dec. 31, 2014. © BHSoftInc PROBIOTIC SUPPLEMENTS AVAILABLE IN CANADA: Indications, Dosage Forms and Clinical Evidence to Date (2014) © BHSoft Inc 2014 INDICATORS FOR ADULT HEALTH Brand Name Genus/Strain Dosage Form CFU/dose Number of doses/day ID AAD CDAD CD-PP TD C IBS IBD-UC IBD-P HP PD LDL-C Align Bifidobacterium longum infantis 35624 Capsules 1B/capsule 1 capsule I1-3 ❄ 5 drops BioGaia drops Lactobacillus reuteri protectis DSM 17938 Drops 100M/5 drops 4 5 6-9 BioGaia chew tabs Chew. tabs 100M/tab 1 tab II II I Regular Capsule 12.5B/capsule Bio-K+ CL1285 ❄ L. acidophilus CL 1285 1-2 capsules L. casei LBC80R Strong Capsule 25B/capsule L. rhamnosus CLR2 “Travel Protection” 30B/capsule 10-12 11,13 a 13-14 a Extra Strenght 50B/capsule I I I Ferm. milk lq./ 50B/tub ½ to 1 tub rice lq./soy lq. Cardioviva L. reuteri NCIMB 30242 Capsule 2B/capsule 1 capsule I18 I15-17 Culturelle Lactobacillus rhamnosus GG Capsule 10B/capsule 1 capsule I19 Florastor Saccharomyces boulardii lyo Capsule, Sachet 5B/capsule/sachet 1-2 caps./sachets I20,21 I13,21,22 I13,14 I23-25 III26 I27-29 Mutaflor ❄ Echerichia Nissle 1917 Capsule 2.5-25B/capsule 1-2 capsules I30-33 L reuteri prodentis PerioBalance (ATCC 55730 and ATCC PTA 5289) Lozenge 100M per/lozenge 2 lozenges II34,35 TuZen L. plantarum 299v Capsule 10B/capsule 1-2 capsules III36 III37 I38-40 L. acidophilus (SD5212), L. casei (SD5218) Sachet 450B/sachet 1-4 sachets VSL#3 ❄ L. bulgaricus (SD5210), L. plantarum (SD5209), B longum (SD5219) II41 I42-44 I43,45-47 B. infantis (SD5220), B. breve (SD5206) S. thermophilus (SD5207) a. Health Canada, Dec 2012 approved claim for Bio-K+100 (NPN 80038453) : “Helps to reduce the risk of Clostridium Difficile Associated Diarrhea (CDAD) in hospitalized patients” PROBIOTIC SUPPLEMENTS AVAILABLE IN CANADA: Indications, Dosage Forms and Clinical Evidence to Date (2014) © BHSoft Inc 2014

INDICATIONS FOR PEDIATRIC HEALTH Brand Name Genus/Strain Dosage CFU/dose Number of Form doses/day Regurg/ Colic ID AAD CDAD IBD-UC HP C IBS/ CID CE GI Mot FAP BioGaia drops ❄ L. reuteri protectis Drops 100M/5 drops 5 drops DSM 17938 Chew. tabs 100M/tab 1 tab BioGaia chew tabs I48,49 I50,51 I52-55 I56 I57 I58 II59 II60

Culturelle Lactobacillus rhamnosus GG Powder 1B/packet 6-10 packets I61-66 I67-68 I69 I70-76

Saccharomyces Capsule 5B/capsule 1-2 capsules 77,78 79 80 28 Florastor boulardii lyo Sachet 5B/sachet 1-2 sachets I I III II

VSL#3 ❄ L. acidophilus (SD5212) Sachet 450B/sachet 1-2 sachets L. casei (SD5218) L. bulgaricus (SD5210) L. plantarum (SD5209) I81 82,83 84 B longum (SD5219) I I B. infantis (SD5220) B. breve (SD5206) S. thermophilus (SD5207) PROBIOTIC SUPPLEMENTS AVAILABLE IN CANADA: Indications, Dosage Forms and Clinical Evidence to Date (2014) © BHSoft Inc 2014 Beausoleil M, Fortier N, Guénette S, et a. Effect of a fermented milk combiningLactobacillus acidophilusCl1285 andLactobacillus caseiin the prevention of antibiotic-associated diarrhea: A randomized, double-blind, placebo-controlled trial . Can J Gastroentero. 2007;21(11):732-6.

INDICATIONS FOR VAGINAL HEALTH Gao XW, et a. Dose-response efficacy of a proprietary probiotic formula ofLactobacillus acidophilusCL1285 and Lactobacillus caseiLBC80R for antibiotic-associated diarrhea and clostridium difficile-associated diarrhea prophylaxis in adult patients. Am J Gastroenterol. 2010;105(7):1636-41. Brenner DM, Chey WD. Bifidobacterium infantis35624: A novel probiotic for the treatment of IBS. Brand Name Probiotic Strain(s) Dosage Form CFU per dose No. of doses Vulvovaginal Bacterial Rev Gastroenterol Disord. 2009;9(1):7-15. Sampalis J, Psaradellis E, Rampakakis E. Efficacy of BIO K+ CL1285 in the reduction of antibiotic-associated per day candidiasis vaginosis diarrhea – a placebo controlled doubleblind randomized, multi-center study.Arch Med Sci 2010; 6: 56–64. Quigley EM, Whorwell PJ, Altringer L, Morel J, O'Mahoney L, Shanahan F. Probiotic use results in normalization of bowel movement frequency in IBS. results from a clinical trial with the novel probioticBifidobacteria infantis35624. Johnston BC, Ma SS, Goldenberg JZ, Thorlund K, Vandvik PO, Loeb M, et al. Probiotics for the prevention Am J Gastroenterol. 2005;100(9 Suppl S):A 326. of Clostridium difficile- associated diarrhea: A systematic review and meta-analysis. Ann Intern Med. 2012. RePhresh ProB L. rhamnosus GR-1, Oral capsule 2.5B each/capsule 1 capsule 85,86 87-89 Whorwell PJ, Altringer L, Morel J, Bond Y, Charbonneau D, O'Mahoney L, et al. Efficacy of an encapsulated Johnson S, Maziade P, McFarlane LV, Trick W, Donskey C, Currie B, et al. Is primary prevention of Clostridium & L. reuteri RC-14 I I probioticBifidobacterium infantis35624 in women with irritable bowel syndrome. Am J Gastroenterol. difficileinfection possible with specific probiotics? Int J Infect Dis. 2012;16(11):e786-92. 2006;101(7):1581-90 Fem-Dophilus Jones ML, Martoni C, Prakash S. Cholesterol lowering and inhibition of sterol absorption by Lactobacillus reuteri Aiello R, Alì Mea. Efficacy and safety ofLactobacillus reuteri ATCC 55730 in preventing acute chemotherapy NCIMB 30242: a randomized controlled trial. European Journal of Clinical Nutrition. 2012 Nov;66(11):1234-41. L. acidophilus A-212 Vaginal capsule 400M/capsule 1-2 capsules induced diarrhoea in colon cancer patients treated with DeGramont or folfox schedule. Ann Oncol. 2008;19 Probaclac BV (suppl 9):abstract B7. Jones ML, Martoni C, Parent M, Prakash S. Cholesterol lowering efficacy of a microencapsulated BSH-active L. rhamnosus A-119 6.8M/capsule 90 Lactobacillus reuteriNCIMB 30242 yoghurt formulation in hypercholesterolemic adults. British Journal of Nutrition. II Cimperman L, Best K, Oster M, et a. A randomized, double-blind, placebo-controlled pilot study ofLactobacillus 2012 May;107(10):1505-13. S. thermophilus A-336 800M/capsule reuterifor the prevention of antibiotic-associated diarrhea in hospitalized adults. J Parenter Enteral Nutr. 2009;33(229):abstract SP-31. Jones ML, Tomaro-Duchesneau C, Martoni C, Prakash S. Cholesterol-lowering with Bile Salt Hydrolase (BSH) active Provacare L. rhamnosus Lcr35 3.41B/capsule 2 capsules 91 92-94 probiotic bacteria, mechanism of action, clinical evidence and future direction for heart health applications. Expert Vaginal capsule I I Ainora M, Nista EC, et a. Impact ofL. reuteri supplementation on anti-H. pylori second line therapy-related. Gut. Opinion on Biological Therapy. 2013 13(5). 2008;57 Suppl II(A327):abstract P1111. Purfem L. rhamnosus PBO1, Vaginal ovule 10B each/ovule 1 ovule Kale-Pradhan PB, Jassal HK, Wilhelm SM. The use ofLactobacillus in the prevention of antibiotic associated L. gasseri EN-153471 (EB01) Francavilla R, Lionetti E, Castellaneta SP, et a. Inhibition ofHeliobacter pyloriinfection in humans byLactobacillus diarrhea: A meta-analysis. Pharmacotherapy. 2010;30(2):119-26. I95,96 reuteriATCC55730 and effect on eradication therapy: A pilot study. Heliobacter. 2008;13:127-34. Armuzzi A, Cremonini F, Bartolozzi F, Canducci F, Candelli M, Ojetti V, et al. The effect of oral administration Imase K, Tanaka A, Tokunaga K, et a. Lactobacillus reuteritablets suppressHeliobacter pyloriinfection –a double of Lactobacillus GG on antibiotic-associated gastrointestinal side effects dutingHeliobacter pylorieradication -blind, randomized, placebo-controlled cross-over clinical study. J Jap Assoc Inf Dis. 2007;81:387-93. therapy. Alimentary Pharmacology & Therapeutics. 2001;15(2):163-9.

Saggioro A, Caroli M, Pasini M, et a. Heliobacter pylorieradication withLactobacillus reuteri. A double blind Can M, Besirbellioglu BA, Avci IY, et a. ProphylacticSaccharomyces boulardiiin the prevention of placebo-controlled study. Dig Liv Dis. 2005;37(Suppl 1):S88. antibiotic-associated diarrhea: A prospective study. Med Sci Monit. 2006;12(4):19-22.

Kruis W, et a. Maintaining remission of ulcerative colitis with the probioticEscherichia coliNissle 1917 is as effective Gionchetti P, et a. Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: Coccorullo P, Strisciuglio P, et a. Lactobacillus reuteri(DSM 17938) in infants with functional chronic constipation: Gawron'ska A, Dziechciarz P, Horvath A, Szajewska H. A randomized, double-blind placebo-controlled trial of Dubey AP, et a. Use of VSL#3® (a new high concentration probiotic mixture) in the treatment of childhood diarrhea as with standard mesalazine. Gut. 2004;53:1617-23. A double-blind, placebo-controlled trial.;119(2):305-9. Gastro. 2000;119(2):305-9. A double-blind, randomized, placebo-controlled study. J Pediatr. 2010;157(4):598-602. LactobacillusGG for abdominal pain disorders in children. Alimentary Pharmacology & Therapeutics. 2007;25(2):177-84. with specific reference to rotavirus diarrhea. J Clin Gastroenterol. 2008;42(Suppl 3 Pt 1):S126-9.

Vivekananda MR, Vandana KL, Bhar KG. Effect of the probiotic Lactobacilli reuteri (Prodentis) in the management Gionchetti P, et a. Prophylaxis of pouchitis onset with probiotic therapy: A double-blind, placebo-controlled trial. Romano C, Ferrau V, et a. Lactobacillus reuteriin children with functional abdominal pain (FAP). J Paediatr Child Doege K, Grajecki D, Zyriax BC, et al. Impact of maternal supplementation with probiotics during pregnancy on Huynh HQ, deBruyn J, Guan L, et a. Probiotic preparation VSL#3 induces remission in children with mild to of periodontal disease: a preliminary randomized clinical trial. Journal of Oral Microbiology 2010, 2: 5344 - DOI: Gastroenterology. 2003;124(5):1202-9. Health. 2010 2010 Jul 8. atopic eczema in childhood—a meta-analysis. Br J Nutr. 2012;107:1–6. moderate acute ulcerative colitis: A pilot study. Inflamm Bowel Dis. 2009;15:760-8. 10.3402/jom.v2i0.5344 Mimura T, Rizzello F, Helwig U, et a. 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Szajewska H, Mrukowicz JZ. Probiotics in the treatment and prevention of acute infectious diarrhea in infants and 2012;51(1):24-30 Klarin B, Wullt M, et a. Lactobacillus plantarum299v reduces colonisation ofClostridium difficilein critically ill Indrio F, Riezzo G, et a. Lactobacillus reuteriaccelerates gastric emptying and improves regurgitation in infants. children: A systematic review of published randomized, double-blind, placebo-controlled trials. J Pediatr Kalliomaki M, Salminen S, Poussa T, et al. Probiotics and prevention of atopic disease: 4-year follow-up patients treated with antibiotics. Acta Anaesthesiologica Scandinavica. 2008;59:1096-102. Eur J Clin Invest. 2012;41(4):417-22. Gastroenterol Nutr. 2001;33(Suppl 2):S17-25. of a randomised placebo-controlled trial. Lancet. 2003;361:1869–1871. Anukam K, Osazuwa E et al. 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Larsson P, Brandsborg E, Forsum U, et a. Extended antimicrobial treatment of bacterial vaginosis combined Hickson M, D'Souza AL, Muthu N, et a. Use of probioticLactobacilluspreparation to prevent diarrhoea associated with humanLactobacillito find the best treatment and minimize the risk of relapses. BMC Infectious Diseases. with antibiotics: Randomised double blind placebo controlled trial. BMJ. 2007;335(7610):80. 2011;11:233. Taipale T, Pienihakkinenen K, Isolauri E, et al.Bifidobacterium animalis subsp. lactis BB-12 in reducing the risk of Oduyebo O, et a. The effects of antimicrobial therapy on bacterial vaginosis in non-pregnany women. Cochrane infections in infancy. Br J Nutr.2011;105:409-416. Collaboration. 2009:1-77. Saavedra JM, Abi-Hanna A, Moore N, et al. Long-term consumption of infant formulas containing live probiotic Agrawal A, Houghton LA, et a. Clinical trial: The effects of a fermented milk product containingBifidobacterium bacteria: tolerance and safety1-3. Am J Clin Nutr. 2004;79:261-7 lactisDN-173 010 on abdominal distension and gastrointestinal transit in irritable bowel syndrome with constipation. Alimentary Pharmacology & Therapeutics. 2008;29:104-1. Corrêa NBO, Filho LAP, Penna FJ, et al. A Randomized Formula Controlled Trial of Bifidobacterium lactis and Streptococcus thermophiles for Prevention of Antibiotic-Associated Diarrhea in Infants. J Clin Gastroenterol. 2005;39(5):385-389. Guyonnet D, Chassany O, Ducrotte P, et al. Effect of a fermented milk containingBifidobacterium animalisDN-173 010 on the health-related quality of life and symptoms in irritable bowel syndrome in adults in Sheu B, Wu JJ, Lo CY, et a. Impact of supplement withLactobacillus-andBifidobacterium-containing yogurt on primary car: A multicenter, randomized, double-blind, controlled trial. Alimentary Pharmacology & triple therapy forHeliobacter pylorieradication. Alimentary Pharmacology & Therapeutics. 2002;16:1669-75. Therapeutics. 2007;1(263):475-86. Sheu B, Cheng H, et a. Pretreatment withLactobacillus-andBifidobacterium-containing yogurt can improve the Yang WX, Mei H, et a. Effect of a fermented milk containingBifidobacterium lactisDN-173010 on chinese efficacy if quadruple therapy in eradicating residualHeliobacter pyloriinfection after failed triple therapy. Am J Clin constipated women. World J Gastroenterol. 2008;14(40):6237-43. Nutr. 2006;83:864-9.

Merestein D, Murphy M, et a. Use of a fermented dairy probiotic drink containing lactobacillus casei (DN-114 Wang KY, Li SN, Liu CS, et a. Effects of ingestingLactobacillus-andBifidobacterium-containing yogurt in subjects 001) to decrease the rate of illness in kids: The DRINK study. A patient-oriented, double-blind, with colonizedHeliobacter pylori.. Am J Clin Nutr. 2004;80(3):737-41. cluster-randomized, placebo-controlled, clinical trial. Eur J Clin Nutr. 2010;64(7):669-77. de Vrese M, Kristen H, Rautenberg P, Laue C, Schrezenmeir J. Probiotic lactobacilli and bifidobacteria in a Pedone CA, Bernabeu AO, Postaire ER, et a. The effect of supplementation with milk fermented by fermented milk product with added fruit preparation Lactobacillus casei(strain DN-114 001) on acute diarrhoea in children attending day care centres. Int J Clin Pract. 1999;53(3):179-84. PROBIOTIC SUPPLEMENTS AVAILABLE IN CANADA: Indications, Dosage Forms and Clinical Evidence to Date (2014) © BHSoft Inc 2014 Beausoleil M, Fortier N, Guénette S, et a. Effect of a fermented milk combiningLactobacillus acidophilusCl1285 andLactobacillus caseiin the prevention of antibiotic-associated diarrhea: A randomized, double-blind, placebo-controlled trial . Can J Gastroentero. 2007;21(11):732-6.

FUNCTIONAL FOODS WITH ADDED PROBIOTICS Gao XW, et a. Dose-response efficacy of a proprietary probiotic formula ofLactobacillus acidophilusCL1285 and Lactobacillus caseiLBC80R for antibiotic-associated diarrhea and clostridium difficile-associated diarrhea prophylaxis in adult patients. Am J Gastroenterol. 2010;105(7):1636-41. CHILDREN ADULTS Brenner DM, Chey WD. Bifidobacterium infantis35624: A novel probiotic for the treatment of IBS. Brand Name Probiotic Strain(s) Dosage Form (CFU) No. of doses/day Rev Gastroenterol Disord. 2009;9(1):7-15. Sampalis J, Psaradellis E, Rampakakis E. Efficacy of BIO K+ CL1285 in the reduction of antibiotic-associated At the time of packaging ID HP AAD CID AAD IBS HP C diarrhea – a placebo controlled doubleblind randomized, multi-center study.Arch Med Sci 2010; 6: 56–64. Quigley EM, Whorwell PJ, Altringer L, Morel J, O'Mahoney L, Shanahan F. Probiotic use results in normalization of bowel movement frequency in IBS. results from a clinical trial with the novel probioticBifidobacteria infantis35624. Johnston BC, Ma SS, Goldenberg JZ, Thorlund K, Vandvik PO, Loeb M, et al. Probiotics for the prevention Bifidobacterium (animalis) 1B bacteria/serving 1-3 servings Am J Gastroenterol. 2005;100(9 Suppl S):A 326. of Clostridium difficile- associated diarrhea: A systematic review and meta-analysis. Ann Intern Med. 2012. Activia ❄ lactis DN-173 010 I97,98 I99 Whorwell PJ, Altringer L, Morel J, Bond Y, Charbonneau D, O'Mahoney L, et al. Efficacy of an encapsulated Johnson S, Maziade P, McFarlane LV, Trick W, Donskey C, Currie B, et al. Is primary prevention of Clostridium Lactobacillus casei probioticBifidobacterium infantis35624 in women with irritable bowel syndrome. Am J Gastroenterol. difficileinfection possible with specific probiotics? Int J Infect Dis. 2012;16(11):e786-92. DanActive ❄ 10B/serving 1-2 servings 100-102 103 104 105 2006;101(7):1581-90 DN-114 001 II II I I Jones ML, Martoni C, Prakash S. Cholesterol lowering and inhibition of sterol absorption by Lactobacillus reuteri Aiello R, Alì Mea. Efficacy and safety ofLactobacillus reuteri ATCC 55730 in preventing acute chemotherapy NCIMB 30242: a randomized controlled trial. European Journal of Clinical Nutrition. 2012 Nov;66(11):1234-41. induced diarrhoea in colon cancer patients treated with DeGramont or folfox schedule. Ann Oncol. 2008;19 Gerber® Bifidobacterium lactis BB-12 1B/ 28 g serving 106 107 1 serving I I (suppl 9):abstract B7. Jones ML, Martoni C, Parent M, Prakash S. Cholesterol lowering efficacy of a microencapsulated BSH-active Infant Cereals DSM 10140 Lactobacillus reuteriNCIMB 30242 yoghurt formulation in hypercholesterolemic adults. British Journal of Nutrition. Gerber® Toddler Cereals 1B/ 35 g serving 1 serving 106 107 Cimperman L, Best K, Oster M, et a. A randomized, double-blind, placebo-controlled pilot study ofLactobacillus 2012 May;107(10):1505-13. I I reuterifor the prevention of antibiotic-associated diarrhea in hospitalized adults. J Parenter Enteral Nutr. Gerber® Graduates 2009;33(229):abstract SP-31. Jones ML, Tomaro-Duchesneau C, Martoni C, Prakash S. Cholesterol-lowering with Bile Salt Hydrolase (BSH) active 1B/ 200mL serving 1 serving I106 I107 probiotic bacteria, mechanism of action, clinical evidence and future direction for heart health applications. Expert Toddler Drink Ainora M, Nista EC, et a. Impact ofL. reuteri supplementation on anti-H. pylori second line therapy-related. Gut. Opinion on Biological Therapy. 2013 13(5). Routine feeding if an alternative 2008;57 Suppl II(A327):abstract P1111. Good Start® 130M/ 100mL serving 108 Kale-Pradhan PB, Jassal HK, Wilhelm SM. The use ofLactobacillus in the prevention of antibiotic associated Probiotic Infant Formula to breast milk is required I Francavilla R, Lionetti E, Castellaneta SP, et a. Inhibition ofHeliobacter pyloriinfection in humans byLactobacillus diarrhea: A meta-analysis. Pharmacotherapy. 2010;30(2):119-26. reuteriATCC55730 and effect on eradication therapy: A pilot study. Heliobacter. 2008;13:127-34. Yoptimal ❄ Bifidobacterium lactis BB-12® 1B/100g 1-2 servings Armuzzi A, Cremonini F, Bartolozzi F, Canducci F, Candelli M, Ojetti V, et al. The effect of oral administration Imase K, Tanaka A, Tokunaga K, et a. Lactobacillus reuteritablets suppressHeliobacter pyloriinfection –a double of Lactobacillus GG on antibiotic-associated gastrointestinal side effects dutingHeliobacter pylorieradication & & I109-112 -blind, randomized, placebo-controlled cross-over clinical study. J Jap Assoc Inf Dis. 2007;81:387-93. therapy. Alimentary Pharmacology & Therapeutics. 2001;15(2):163-9. iOGO Probio ❄ Lactobacillus acidophilus LA-5 Saggioro A, Caroli M, Pasini M, et a. Heliobacter pylorieradication withLactobacillus reuteri. A double blind Can M, Besirbellioglu BA, Avci IY, et a. ProphylacticSaccharomyces boulardiiin the prevention of placebo-controlled study. Dig Liv Dis. 2005;37(Suppl 1):S88. antibiotic-associated diarrhea: A prospective study. Med Sci Monit. 2006;12(4):19-22.

Merestein D, Murphy M, et a. Use of a fermented dairy probiotic drink containing lactobacillus casei (DN-114 Wang KY, Li SN, Liu CS, et a. Effects of ingestingLactobacillus-andBifidobacterium-containing yogurt in subjects 001) to decrease the rate of illness in kids: The DRINK study. A patient-oriented, double-blind, with colonizedHeliobacter pylori.. Am J Clin Nutr. 2004;80(3):737-41. cluster-randomized, placebo-controlled, clinical trial. Eur J Clin Nutr. 2010;64(7):669-77. de Vrese M, Kristen H, Rautenberg P, Laue C, Schrezenmeir J. Probiotic lactobacilli and bifidobacteria in a Pedone CA, Bernabeu AO, Postaire ER, et a. The effect of supplementation with milk fermented by fermented milk product with added fruit preparation Lactobacillus casei(strain DN-114 001) on acute diarrhoea in children attending day care centres. Int J Clin Pract. 1999;53(3):179-84. 10. Beausoleil M, Fortier N, Guénette S, et a. Effect of a fermented milk combiningLactobacillus acidophilusCl1285 andLactobacillus caseiin the prevention of antibiotic-associated diarrhea: A randomized, double-blind, placebo-controlled trial . Can J Gastroentero. 2007;21(11):732-6.

REFERENCES 11. Gao XW, et a. Dose-response efficacy of a proprietary probiotic formula ofLactobacillus acidophilusCL1285 and Lactobacillus caseiLBC80R for antibiotic-associated diarrhea and clostridium difficile-associated diarrhea prophylaxis in adult patients. Am J Gastroenterol. 2010;105(7):1636-41. 1. Brenner DM, Chey WD. Bifidobacterium infantis35624: A novel probiotic for the treatment of IBS. Rev Gastroenterol Disord. 2009;9(1):7-15. 12. Sampalis J, Psaradellis E, Rampakakis E. Efficacy of BIO K+ CL1285 in the reduction of antibiotic-associated diarrhea – a placebo controlled doubleblind randomized, multi-center study.Arch Med Sci 2010; 6: 56–64. 2. Quigley EM, Whorwell PJ, Altringer L, Morel J, O'Mahoney L, Shanahan F. Probiotic use results in normalization of bowel movement frequency in IBS. results from a clinical trial with the novel probioticBifidobacteria infantis35624. 13. Johnston BC, Ma SS, Goldenberg JZ, Thorlund K, Vandvik PO, Loeb M, et al. Probiotics for the prevention Am J Gastroenterol. 2005;100(9 Suppl S):A 326. of Clostridium difficile- associated diarrhea: A systematic review and meta-analysis. Ann Intern Med. 2012.

3. Whorwell PJ, Altringer L, Morel J, Bond Y, Charbonneau D, O'Mahoney L, et al. Efficacy of an encapsulated 14. Johnson S, Maziade P, McFarlane LV, Trick W, Donskey C, Currie B, et al. Is primary prevention of Clostridium probioticBifidobacterium infantis35624 in women with irritable bowel syndrome. Am J Gastroenterol. difficileinfection possible with specific probiotics? Int J Infect Dis. 2012;16(11):e786-92. 2006;101(7):1581-90 15. Jones ML, Martoni C, Prakash S. Cholesterol lowering and inhibition of sterol absorption by Lactobacillus reuteri 4. Aiello R, Alì Mea. Efficacy and safety ofLactobacillus reuteri ATCC 55730 in preventing acute chemotherapy NCIMB 30242: a randomized controlled trial. European Journal of Clinical Nutrition. 2012 Nov;66(11):1234-41. induced diarrhoea in colon cancer patients treated with DeGramont or folfox schedule. Ann Oncol. 2008;19 (suppl 9):abstract B7. 16. Jones ML, Martoni C, Parent M, Prakash S. Cholesterol lowering efficacy of a microencapsulated BSH-active Lactobacillus reuteriNCIMB 30242 yoghurt formulation in hypercholesterolemic adults. British Journal of Nutrition. 5. Cimperman L, Best K, Oster M, et a. A randomized, double-blind, placebo-controlled pilot study ofLactobacillus 2012 May;107(10):1505-13. reuterifor the prevention of antibiotic-associated diarrhea in hospitalized adults. J Parenter Enteral Nutr. 2009;33(229):abstract SP-31. 17. Jones ML, Tomaro-Duchesneau C, Martoni C, Prakash S. Cholesterol-lowering with Bile Salt Hydrolase (BSH) active probiotic bacteria, mechanism of action, clinical evidence and future direction for heart health applications. Expert 6. Ainora M, Nista EC, et a. Impact ofL. reuteri supplementation on anti-H. pylori second line therapy-related. Gut. Opinion on Biological Therapy. 2013 13(5). 2008;57 Suppl II(A327):abstract P1111. 18. Kale-Pradhan PB, Jassal HK, Wilhelm SM. The use ofLactobacillus in the prevention of antibiotic associated 7. Francavilla R, Lionetti E, Castellaneta SP, et a. Inhibition ofHeliobacter pyloriinfection in humans byLactobacillus diarrhea: A meta-analysis. Pharmacotherapy. 2010;30(2):119-26. reuteriATCC55730 and effect on eradication therapy: A pilot study. Heliobacter. 2008;13:127-34. 19. Armuzzi A, Cremonini F, Bartolozzi F, Canducci F, Candelli M, Ojetti V, et al. The effect of oral administration 8. Imase K, Tanaka A, Tokunaga K, et a. Lactobacillus reuteritablets suppressHeliobacter pyloriinfection –a double of Lactobacillus GG on antibiotic-associated gastrointestinal side effects dutingHeliobacter pylorieradication -blind, randomized, placebo-controlled cross-over clinical study. J Jap Assoc Inf Dis. 2007;81:387-93. therapy. Alimentary Pharmacology & Therapeutics. 2001;15(2):163-9.

9. Saggioro A, Caroli M, Pasini M, et a. Heliobacter pylorieradication withLactobacillus reuteri. A double blind 20. Can M, Besirbellioglu BA, Avci IY, et a. ProphylacticSaccharomyces boulardiiin the prevention of placebo-controlled study. Dig Liv Dis. 2005;37(Suppl 1):S88. antibiotic-associated diarrhea: A prospective study. Med Sci Monit. 2006;12(4):19-22.

Merestein D, Murphy M, et a. Use of a fermented dairy probiotic drink containing lactobacillus casei (DN-114 Wang KY, Li SN, Liu CS, et a. Effects of ingestingLactobacillus-andBifidobacterium-containing yogurt in subjects 001) to decrease the rate of illness in kids: The DRINK study. A patient-oriented, double-blind, with colonizedHeliobacter pylori.. Am J Clin Nutr. 2004;80(3):737-41. cluster-randomized, placebo-controlled, clinical trial. Eur J Clin Nutr. 2010;64(7):669-77. de Vrese M, Kristen H, Rautenberg P, Laue C, Schrezenmeir J. Probiotic lactobacilli and bifidobacteria in a Pedone CA, Bernabeu AO, Postaire ER, et a. The effect of supplementation with milk fermented by fermented milk product with added fruit preparation Lactobacillus casei(strain DN-114 001) on acute diarrhoea in children attending day care centres. Int J Clin Pract. 1999;53(3):179-84. Beausoleil M, Fortier N, Guénette S, et a. Effect of a fermented milk combiningLactobacillus acidophilusCl1285 andLactobacillus caseiin the prevention of antibiotic-associated diarrhea: A randomized, double-blind, placebo-controlled trial . Can J Gastroentero. 2007;21(11):732-6.

Gao XW, et a. Dose-response efficacy of a proprietary probiotic formula ofLactobacillus acidophilusCL1285 and Lactobacillus caseiLBC80R for antibiotic-associated diarrhea and clostridium difficile-associated diarrhea prophylaxis in adult patients. Am J Gastroenterol. 2010;105(7):1636-41. Brenner DM, Chey WD. Bifidobacterium infantis35624: A novel probiotic for the treatment of IBS. Rev Gastroenterol Disord. 2009;9(1):7-15. Sampalis J, Psaradellis E, Rampakakis E. Efficacy of BIO K+ CL1285 in the reduction of antibiotic-associated diarrhea – a placebo controlled doubleblind randomized, multi-center study.Arch Med Sci 2010; 6: 56–64. Quigley EM, Whorwell PJ, Altringer L, Morel J, O'Mahoney L, Shanahan F. Probiotic use results in normalization of bowel movement frequency in IBS. results from a clinical trial with the novel probioticBifidobacteria infantis35624. Johnston BC, Ma SS, Goldenberg JZ, Thorlund K, Vandvik PO, Loeb M, et al. Probiotics for the prevention Am J Gastroenterol. 2005;100(9 Suppl S):A 326. of Clostridium difficile- associated diarrhea: A systematic review and meta-analysis. Ann Intern Med. 2012.

Whorwell PJ, Altringer L, Morel J, Bond Y, Charbonneau D, O'Mahoney L, et al. Efficacy of an encapsulated Johnson S, Maziade P, McFarlane LV, Trick W, Donskey C, Currie B, et al. Is primary prevention of Clostridium probioticBifidobacterium infantis35624 in women with irritable bowel syndrome. Am J Gastroenterol. difficileinfection possible with specific probiotics? Int J Infect Dis. 2012;16(11):e786-92. 2006;101(7):1581-90 Jones ML, Martoni C, Prakash S. Cholesterol lowering and inhibition of sterol absorption by Lactobacillus reuteri Aiello R, Alì Mea. Efficacy and safety ofLactobacillus reuteri ATCC 55730 in preventing acute chemotherapy NCIMB 30242: a randomized controlled trial. European Journal of Clinical Nutrition. 2012 Nov;66(11):1234-41. induced diarrhoea in colon cancer patients treated with DeGramont or folfox schedule. Ann Oncol. 2008;19 (suppl 9):abstract B7. Jones ML, Martoni C, Parent M, Prakash S. Cholesterol lowering efficacy of a microencapsulated BSH-active Lactobacillus reuteriNCIMB 30242 yoghurt formulation in hypercholesterolemic adults. British Journal of Nutrition. Cimperman L, Best K, Oster M, et a. A randomized, double-blind, placebo-controlled pilot study ofLactobacillus 2012 May;107(10):1505-13. reuterifor the prevention of antibiotic-associated diarrhea in hospitalized adults. J Parenter Enteral Nutr. 2009;33(229):abstract SP-31. Jones ML, Tomaro-Duchesneau C, Martoni C, Prakash S. Cholesterol-lowering with Bile Salt Hydrolase (BSH) active probiotic bacteria, mechanism of action, clinical evidence and future direction for heart health applications. Expert Ainora M, Nista EC, et a. Impact ofL. reuteri supplementation on anti-H. pylori second line therapy-related. Gut. Opinion on Biological Therapy. 2013 13(5). 2008;57 Suppl II(A327):abstract P1111. Kale-Pradhan PB, Jassal HK, Wilhelm SM. The use ofLactobacillus in the prevention of antibiotic associated Francavilla R, Lionetti E, Castellaneta SP, et a. Inhibition ofHeliobacter pyloriinfection in humans byLactobacillus diarrhea: A meta-analysis. Pharmacotherapy. 2010;30(2):119-26. reuteriATCC55730 and effect on eradication therapy: A pilot study. Heliobacter. 2008;13:127-34. Armuzzi A, Cremonini F, Bartolozzi F, Canducci F, Candelli M, Ojetti V, et al. The effect of oral administration Imase K, Tanaka A, Tokunaga K, et a. Lactobacillus reuteritablets suppressHeliobacter pyloriinfection –a double of Lactobacillus GG on antibiotic-associated gastrointestinal side effects dutingHeliobacter pylorieradication -blind, randomized, placebo-controlled cross-over clinical study. J Jap Assoc Inf Dis. 2007;81:387-93. therapy. Alimentary Pharmacology & Therapeutics. 2001;15(2):163-9.

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Guandalini S, Pensabene L, Zikri MA, Dias JA, Casali LB, Hoekstra H, et al.Lactobacillus GG administered in oral a randomized controlled trial. Allergy 2011; 66: 509–516. vaginal gel to treat symptomatic bacterialvaginosis. Microbes and Infection. 2006;8(12-13):2772-6. and side eddects during treatment. Alimentary Pharmacology & Therapeutics. 2010;32(9):1069-7. of irritable bowel syndrome. World J Gastroenterol. 2012;18(30):4012-8. rehydration solution to children with acute diarrhoea: a multicenter European trial. Journal of Pediatric Shornikova AV, Casa IA, Isolauri, et a. Lactobacillus reuterias a therapeutic agent in acute diarrhea in young Gastroenterology and Nutrition 2000;30(1):54–60. Htwe K, Yee KS, Tin M, et a. Effect ofSaccharomyces boulardiiin the treatment of acute watery diarrhea in myanmar Hummelen R, Changalucha J, Butamanya NL, et a. Lactobacillus rhamnosusGR-1 andL. reuteriRC-14 to prevent or 29. Cindoruk M, Erkan G, Karakan T, Dursun A, Unal S. Efficacy and safety of Saccharomyces boulardii in the 14-day 41. Parkes GC, Chatoor D, Emmanuel A. The probiotic VSL#3 increases scbm and reduces symptom severity scores children: A prospective, randomized, placebo-controlled study. J Pediatr Gastroenterol Nutr. 1997;24:399-404. children: A randomized controlled study. Am J Trop Med Hyg. 2008;78:214-6. cure bacterial vaginosis among women with HIV. Int J Gynaecol Obstet. 2010;111(3):254-8. triple anti-Helicobacter pylori therapy: a prospective randomized placebo-controlled double-blind study. in patients with functional constipation. Gut. 2011;60:163. Ritchie BK, Brewster DR, Tran CD, Davidson GP, McNeil Y, Butler RN. Efficacy of Lactobacillus GG in Aboriginal Helicobacter 2007; 12: 309–16. Agustina R, Kok FJ, van de Rest O, Fahmida U, Firmansya A, Lukito W, et al. Randomized trial of probiotics and children with acute diarrhoeal disease: a randomised clinical trial. Journal of Pediatric Gastroenterology and Kurugol Z, Koturoglu G. Effects ofSaccharomyces boulardiiin children with acute diarrhea. Acta Paediatrica. Reid G, Bruce AW, Fraser N, et a. Oral probiotics can resolve urogenital infections. FEMS Immunol Med Microbiol. 42. Sood A, Midha V, Makharia GK, et a. The probiotic preparation VSL#3 induces remission in patients with calcium on diarrhea and respiratory tract infections in indonesian children. Pediatrics. 2012;29(5):1-10. Nutrition 2010;50(6):619–24. 2005;94:44-7. 2001;30:49-52. 30. Floch MH. 1. editorials.doi: 10.1097/MCG.0b013e3181cf837f. Journal of Clinical Gastroenterology. mild-to-moderately active ulcerative colitis. Clin Gastroenterol Hepatol. 2009;11:1202-9. Misra S, Sabui TK, Pal NK. A randomized controlled trial to evaluate the efficacy of Lactobacillus GG in infantile 2010;44(4):237-8. Francavilla R, Lionetti E, Castellaneta SP, et a. Randomised clinical trial: Lactobacillus reuteri DSM 17938 vs.placebo Kotowska M, Albrecht P, Szajewska H. Saccharomyces boulardiiin the prevention of antibiotic-associated diarrhea Ya, W., Reifer, C. and Miller, L. E. 2010. Efficacy of vaginal probiotic capsules for recurrent bacterial vaginosis: 43. Tursi A, Brandimarte G, Giorgetti GM, et a. Low-dose balsalazide plus a high-potency probiotic preparation is in children with acute diarrhoea - a double-blind study. Alimentary Pharmacology & Therapeutics. diarrhea. The Journal of Pediatrics 2009;155(1):129–32. more effective than balsalazide alone or mesalazine in the treatment of acute mild-to-moderate ulcerative colitis. 2012;36(4):363-9. in children: A randomized double-blind placebo-controlled trial. Alimentary Pharmacology & Therapeutics. a double-blind, randomized, placebo-controlled study. American journal of obstetrics and gynecology, 203 (2), 31. Henker J, Muller S., Laass M, et a. ProbioticEscherichia coliNissle 1917 (EcN) for successful remission maintenance 2005;21(5):583-90. pp. 120--1. of ulcerative colitis in children and adolescents: An open-label pilot study. Zeitschrift fuer Gastroenterologie. Med Sci Monit. 2004;10(11):PI126-31. Vanderhoof JA, Whitney DB, Antonson DL, Hanner TL, Lupo JV, Young RJ. Lactobacillus GG in the prevention of 2008;46(9):874-5. Lionetti E, Minielle VL, Castellaneta SP, et a. Lactobacillus reuteritherapy to reduce side effects during antibiotic-associated diarrhea in children. J Pediatr. 1999;135:564-8. 44. Tursi A, Brandimarte G, Papa A, et a. Treatment of relapsing mild-to-moderate ulcerative colitis with the probiotic anti-Heliobacter pyloritreatment in children: A randomized placebo controlled trial. Alimentary Pharmacology & Buts JP, Corthier G, Delmee M. Saccharomyces boulardiiforClostridium difficile-associated enteropathies in Kern AM, Bohbot JM, Cardot JM. Preventive treatment of vulvovaginal candidosis with vaginal probiotic infants. J Pediatr Gastroenterol Nutr. 1993;16:419-25. (gynophilus®-lcr regenerans®): Results of the observational study candiflore. La Lettre du Gynecologue. 32. VSL#3 as adjunctive to a standard pharmaceutical treatment: A double-blind, randomized, placebo-controlled Therapeutics. 2006;24:1461-8. Johnston BC, Goldenberg JZ, Vandvik PO, Sun X, Guyatt GH. Probiotics for the prevention of Kruis W, et a. Double-blind comparison of an oralEscherichia colipreparation and mesalazine in maintaining study. Am J Gastroenterol. 2010;105(2218):2227. pediatricantibiotic-associated diarrhea. Cochrane Database Syst Rev. 2011;11:CD004827. 2012;370:33-7. remission of ulcerative colitis. Alimentary Pharmacology & Therapeutics. 1997;11:853-8.

Merestein D, Murphy M, et a. Use of a fermented dairy probiotic drink containing lactobacillus casei (DN-114 Wang KY, Li SN, Liu CS, et a. Effects of ingestingLactobacillus-andBifidobacterium-containing yogurt in subjects 001) to decrease the rate of illness in kids: The DRINK study. A patient-oriented, double-blind, with colonizedHeliobacter pylori.. Am J Clin Nutr. 2004;80(3):737-41. cluster-randomized, placebo-controlled, clinical trial. Eur J Clin Nutr. 2010;64(7):669-77. de Vrese M, Kristen H, Rautenberg P, Laue C, Schrezenmeir J. Probiotic lactobacilli and bifidobacteria in a Pedone CA, Bernabeu AO, Postaire ER, et a. The effect of supplementation with milk fermented by fermented milk product with added fruit preparation Lactobacillus casei(strain DN-114 001) on acute diarrhoea in children attending day care centres. Int J Clin Pract. 1999;53(3):179-84. Beausoleil M, Fortier N, Guénette S, et a. Effect of a fermented milk combiningLactobacillus acidophilusCl1285 andLactobacillus caseiin the prevention of antibiotic-associated diarrhea: A randomized, double-blind, placebo-controlled trial . Can J Gastroentero. 2007;21(11):732-6.

Kruis W, et a. Maintaining remission of ulcerative colitis with the probioticEscherichia coliNissle 1917 is as effective 45. Gionchetti P, et a. Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: 57. Coccorullo P, Strisciuglio P, et a. Lactobacillus reuteri(DSM 17938) in infants with functional chronic constipation: Gawron'ska A, Dziechciarz P, Horvath A, Szajewska H. A randomized, double-blind placebo-controlled trial of Dubey AP, et a. Use of VSL#3® (a new high concentration probiotic mixture) in the treatment of childhood diarrhea as with standard mesalazine. Gut. 2004;53:1617-23. A double-blind, placebo-controlled trial.;119(2):305-9. Gastro. 2000;119(2):305-9. A double-blind, randomized, placebo-controlled study. J Pediatr. 2010;157(4):598-602. LactobacillusGG for abdominal pain disorders in children. Alimentary Pharmacology & Therapeutics. 2007;25(2):177-84. with specific reference to rotavirus diarrhea. J Clin Gastroenterol. 2008;42(Suppl 3 Pt 1):S126-9.

Vivekananda MR, Vandana KL, Bhar KG. Effect of the probiotic Lactobacilli reuteri (Prodentis) in the management 46. Gionchetti P, et a. Prophylaxis of pouchitis onset with probiotic therapy: A double-blind, placebo-controlled trial. 58. Romano C, Ferrau V, et a. Lactobacillus reuteriin children with functional abdominal pain (FAP). J Paediatr Child Doege K, Grajecki D, Zyriax BC, et al. Impact of maternal supplementation with probiotics during pregnancy on Huynh HQ, deBruyn J, Guan L, et a. Probiotic preparation VSL#3 induces remission in children with mild to of periodontal disease: a preliminary randomized clinical trial. Journal of Oral Microbiology 2010, 2: 5344 - DOI: Gastroenterology. 2003;124(5):1202-9. Health. 2010 2010 Jul 8. atopic eczema in childhood—a meta-analysis. Br J Nutr. 2012;107:1–6. moderate acute ulcerative colitis: A pilot study. Inflamm Bowel Dis. 2009;15:760-8. 10.3402/jom.v2i0.5344 47. Mimura T, Rizzello F, Helwig U, et a. Once daily high dose probiotic therapy (VSL#3) for maintaining remission 59. Weizman Z, Asli G, Alsheikh A. Effect of a probiotic infant formula on infections in child care centers: Comparison Kalliomaki M, Salminen S, Arvilommi H, et al. Probiotics in primary prevention of atopic disease: a randomised Miele E, Pascarella F, Giannetti E, et a. Effect of a probiotic preparation (VSL#3) on induction and maintenance of Twetman S et al. Short-term effect of chewing gums containing probiotic Lactobacillus reuteri on the levels in recurrent or refractory pouchitis. Gut. 2004;53:108-14. of two probiotic agents. Pediatrics 2005;115(1):5-9. placebo controlled trial. Lancet. 2001;357:1076–1079. remission in children with ulcerative colitis. Am J Gastroenterol. 2009;104:437-43. of inflammatory mediators in gingival crevicular fluid. Acta Odontol Scand. 67(1):19–24. 48. Indrio F, Riezzo G, Raimondi F, et a. The effect of probiotics on feeding tolerance, bowel habits, and 60. Abrahamsson TR, Jakobsson T, Bo¨ ttcher MF, et al. Probiotics in prevention of IgE associated eczema: a Rautava S, Kalliomaki M, Isolauri E. Probiotics during pregnancy and breast-feeding might confer Guandalini S, Magazzù G, Chiaro A, et al. VSL#3 improves symptoms in children with irritable bowel syndrom: A double-blind, randomized, placebo-controlled trial. J Allergy Clin Immunol 2007; 119: 1174–1180. Lonnermark E, Friman V, Lappas G, et a. Intake ofLactobacillus plantarumreduces certain gastrointestinal gastrointestinal motility in preterm newborns, a double-blind, placebo-controlled pilot study. J Pediatr. immunomodulatory protection against atopic disease in the infant. J Allergy Clin Immunol. 2002;109:119–121. multicenter, randomized, placebo-controlled, double-blind, crossover study. J Pediatr Gastroenterol Nutr. symptoms during treatment with antibiotics. J Clin Gastroenterol. 2010;44(2):106-12. 2008;152:801-6. 61. Szajewska H, Mrukowicz JZ. Probiotics in the treatment and prevention of acute infectious diarrhea in infants and 2012;51(1):24-30 Klarin B, Wullt M, et a. Lactobacillus plantarum299v reduces colonisation ofClostridium difficilein critically ill 49. Indrio F, Riezzo G, et a. Lactobacillus reuteriaccelerates gastric emptying and improves regurgitation in infants. children: A systematic review of published randomized, double-blind, placebo-controlled trials. J Pediatr Kalliomaki M, Salminen S, Poussa T, et al. Probiotics and prevention of atopic disease: 4-year follow-up patients treated with antibiotics. Acta Anaesthesiologica Scandinavica. 2008;59:1096-102. Eur J Clin Invest. 2012;41(4):417-22. Gastroenterol Nutr. 2001;33(Suppl 2):S17-25. of a randomised placebo-controlled trial. Lancet. 2003;361:1869–1871. Anukam K, Osazuwa E et al. Augmentation of antimicrobial metronidazole therapy of bacterial vaginosis with oral 62. probioticLactobacillus rhamnosusGR-1 andLactobacillus reuteriRC-14: Randomized, double-blind, placebo Niedzielin K, Korodecki H, Birkenfeld B. A controlled, double-blind, randomized study on the efficacy of 50. Savino F, Pelle E, Palumeri E, et a. Lactobacillus reuteri(ATCC 55730) versus simethicone in the treatment of Basu S, Chatterjee M, Ganguly S, Chandra P.K. Efficacy of Lactobacillus rhamnosus GG in acute watery diarrhoea of Kalliomaki M, Salminen S, Poussa T, et al. Probiotics during the first 7 years of life: a cumulative risk reduction controlled trial. Microbes and Infection. 2006;8:1450-4. Lactobacillus plantarum299V in patients with irritable bowel syndrome. Eur J Gastroenterol Hepatol. infantile colic: A prospective randomized study. Pediatrics. 2007;119:124-30. Indian children: a randomised controlled trial. Journal of Paediatrics and Child Health 2007;43(12):837–42. of eczema in a randomized, placebo controlled trial. J Allergy Clin Immunol. 2007;119:1019–1021. 2001;13(10):1143-7. Reid G, Charbonneau D, Erb J, Kochanowski B, Beuerman D, Poehner R, et al. Oral use ofLactobacillus 51. Savino F, Cordisco L, et a. Lactobacillus reuteriDSM 17 938 in infantile colic: A randomized, double-blind, 63. Basu S, Paul DK, Ganguly S, Chatterjee M, Chandra PK. Efficacy of high-dose Lactobacillus rhamnosus GG in Dotterud C, Storrø O, Johnsen R, et al. Probiotics in pregnant women to prevent allergic disease: a randomized, rhamnosusGR-1 andL. fermentumRC-14 significantly alters vaginal flora: Randomized, placebo-controlled trial in 64 Nobaek S, Johansson ML, Molin G, et a. Alteration of intestinal microflora is associated with reduction in placebo-controlled study. Pediatrics. 2010;126(3):e526-533. controlling acute watery diarrhea in Indian children: a randomized controlled trial. Journal of Clinical double-blind trial. Br J Dermatol 2010; 163: 616–623 healthy women. FEMS Immunol Med Microbiol. 2003;35:131-4. abdominal bloating and pain in patients with irritable bowel syndrome. Am J Gastroenterol. 2000;95:1231. Gastroenterology 2009;43(3):208–13. 52. Eom TH, Oh EY, Kim YH, et a. The therapeutic effect ofLactobacillus reuteriin acute diarrhea in infants and toddlers Boyle RJ, Ismail IH, Kivivuori S, et al. Lactobacillus GG treatment during pregnancy for the prevention of eczema: Anukam K, Osazuwa E et al. Clinical study comparing probioticLactobacillusGR-1 and RC-14 with metronidazole Ducrotte P, Sawant PD, Jayanthi V. Clinical trial: Lactobacillus plantarum 299v (DSM 9843) improves symptoms : A prospective, randomized, placebo-controlled study. Korean J Ped. 2005;48:986-9. 64. Guandalini S, Pensabene L, Zikri MA, Dias JA, Casali LB, Hoekstra H, et al.Lactobacillus GG administered in oral a randomized controlled trial. Allergy 2011; 66: 509–516. vaginal gel to treat symptomatic bacterialvaginosis. Microbes and Infection. 2006;8(12-13):2772-6. of irritable bowel syndrome. World J Gastroenterol. 2012;18(30):4012-8. rehydration solution to children with acute diarrhoea: a multicenter European trial. Journal of Pediatric 53. Shornikova AV, Casa IA, Isolauri, et a. Lactobacillus reuterias a therapeutic agent in acute diarrhea in young Gastroenterology and Nutrition 2000;30(1):54–60. Htwe K, Yee KS, Tin M, et a. Effect ofSaccharomyces boulardiiin the treatment of acute watery diarrhea in myanmar Hummelen R, Changalucha J, Butamanya NL, et a. Lactobacillus rhamnosusGR-1 andL. reuteriRC-14 to prevent or Parkes GC, Chatoor D, Emmanuel A. The probiotic VSL#3 increases scbm and reduces symptom severity scores children: A prospective, randomized, placebo-controlled study. J Pediatr Gastroenterol Nutr. 1997;24:399-404. children: A randomized controlled study. Am J Trop Med Hyg. 2008;78:214-6. cure bacterial vaginosis among women with HIV. Int J Gynaecol Obstet. 2010;111(3):254-8. in patients with functional constipation. Gut. 2011;60:163. 65. Ritchie BK, Brewster DR, Tran CD, Davidson GP, McNeil Y, Butler RN. Efficacy of Lactobacillus GG in Aboriginal 54. Agustina R, Kok FJ, van de Rest O, Fahmida U, Firmansya A, Lukito W, et al. Randomized trial of probiotics and children with acute diarrhoeal disease: a randomised clinical trial. Journal of Pediatric Gastroenterology and Kurugol Z, Koturoglu G. Effects ofSaccharomyces boulardiiin children with acute diarrhea. Acta Paediatrica. Reid G, Bruce AW, Fraser N, et a. Oral probiotics can resolve urogenital infections. FEMS Immunol Med Microbiol. Sood A, Midha V, Makharia GK, et a. The probiotic preparation VSL#3 induces remission in patients with calcium on diarrhea and respiratory tract infections in indonesian children. Pediatrics. 2012;29(5):1-10. Nutrition 2010;50(6):619–24. 2005;94:44-7. 2001;30:49-52. mild-to-moderately active ulcerative colitis. Clin Gastroenterol Hepatol. 2009;11:1202-9. 55. Misra S, Sabui TK, Pal NK. A randomized controlled trial to evaluate the efficacy of Lactobacillus GG in infantile Francavilla R, Lionetti E, Castellaneta SP, et a. Randomised clinical trial: Lactobacillus reuteri DSM 17938 vs.placebo 66. Kotowska M, Albrecht P, Szajewska H. Saccharomyces boulardiiin the prevention of antibiotic-associated diarrhea Ya, W., Reifer, C. and Miller, L. E. 2010. Efficacy of vaginal probiotic capsules for recurrent bacterial vaginosis: Tursi A, Brandimarte G, Giorgetti GM, et a. Low-dose balsalazide plus a high-potency probiotic preparation is in children with acute diarrhoea - a double-blind study. Alimentary Pharmacology & Therapeutics. diarrhea. The Journal of Pediatrics 2009;155(1):129–32. more effective than balsalazide alone or mesalazine in the treatment of acute mild-to-moderate ulcerative colitis. 2012;36(4):363-9. in children: A randomized double-blind placebo-controlled trial. Alimentary Pharmacology & Therapeutics. a double-blind, randomized, placebo-controlled study. American journal of obstetrics and gynecology, 203 (2), Med Sci Monit. 2004;10(11):PI126-31. 67. Vanderhoof JA, Whitney DB, Antonson DL, Hanner TL, Lupo JV, Young RJ. Lactobacillus GG in the prevention of 2005;21(5):583-90. pp. 120--1. 56. Lionetti E, Minielle VL, Castellaneta SP, et a. Lactobacillus reuteritherapy to reduce side effects during antibiotic-associated diarrhea in children. J Pediatr. 1999;135:564-8. Tursi A, Brandimarte G, Papa A, et a. Treatment of relapsing mild-to-moderate ulcerative colitis with the probiotic anti-Heliobacter pyloritreatment in children: A randomized placebo controlled trial. Alimentary Pharmacology & Buts JP, Corthier G, Delmee M. Saccharomyces boulardiiforClostridium difficile-associated enteropathies in Kern AM, Bohbot JM, Cardot JM. Preventive treatment of vulvovaginal candidosis with vaginal probiotic VSL#3 as adjunctive to a standard pharmaceutical treatment: A double-blind, randomized, placebo-controlled Therapeutics. 2006;24:1461-8. 68. Johnston BC, Goldenberg JZ, Vandvik PO, Sun X, Guyatt GH. Probiotics for the prevention of infants. J Pediatr Gastroenterol Nutr. 1993;16:419-25. (gynophilus®-lcr regenerans®): Results of the observational study candiflore. La Lettre du Gynecologue. study. Am J Gastroenterol. 2010;105(2218):2227. pediatricantibiotic-associated diarrhea. Cochrane Database Syst Rev. 2011;11:CD004827. 2012;370:33-7.

Merestein D, Murphy M, et a. Use of a fermented dairy probiotic drink containing lactobacillus casei (DN-114 Wang KY, Li SN, Liu CS, et a. Effects of ingestingLactobacillus-andBifidobacterium-containing yogurt in subjects 001) to decrease the rate of illness in kids: The DRINK study. A patient-oriented, double-blind, with colonizedHeliobacter pylori.. Am J Clin Nutr. 2004;80(3):737-41. cluster-randomized, placebo-controlled, clinical trial. Eur J Clin Nutr. 2010;64(7):669-77. de Vrese M, Kristen H, Rautenberg P, Laue C, Schrezenmeir J. Probiotic lactobacilli and bifidobacteria in a Pedone CA, Bernabeu AO, Postaire ER, et a. The effect of supplementation with milk fermented by fermented milk product with added fruit preparation Lactobacillus casei(strain DN-114 001) on acute diarrhoea in children attending day care centres. Int J Clin Pract. 1999;53(3):179-84. Beausoleil M, Fortier N, Guénette S, et a. Effect of a fermented milk combiningLactobacillus acidophilusCl1285 andLactobacillus caseiin the prevention of antibiotic-associated diarrhea: A randomized, double-blind, placebo-controlled trial . Can J Gastroentero. 2007;21(11):732-6.

Kruis W, et a. Maintaining remission of ulcerative colitis with the probioticEscherichia coliNissle 1917 is as effective Gionchetti P, et a. Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: Coccorullo P, Strisciuglio P, et a. Lactobacillus reuteri(DSM 17938) in infants with functional chronic constipation: 69. Gawron'ska A, Dziechciarz P, Horvath A, Szajewska H. A randomized, double-blind placebo-controlled trial of 81. Dubey AP, et a. Use of VSL#3® (a new high concentration probiotic mixture) in the treatment of childhood diarrhea as with standard mesalazine. Gut. 2004;53:1617-23. A double-blind, placebo-controlled trial.;119(2):305-9. Gastro. 2000;119(2):305-9. A double-blind, randomized, placebo-controlled study. J Pediatr. 2010;157(4):598-602. LactobacillusGG for abdominal pain disorders in children. Alimentary Pharmacology & Therapeutics. 2007;25(2):177-84. with specific reference to rotavirus diarrhea. J Clin Gastroenterol. 2008;42(Suppl 3 Pt 1):S126-9.

Vivekananda MR, Vandana KL, Bhar KG. Effect of the probiotic Lactobacilli reuteri (Prodentis) in the management Gionchetti P, et a. Prophylaxis of pouchitis onset with probiotic therapy: A double-blind, placebo-controlled trial. Romano C, Ferrau V, et a. Lactobacillus reuteriin children with functional abdominal pain (FAP). J Paediatr Child 70. Doege K, Grajecki D, Zyriax BC, et al. Impact of maternal supplementation with probiotics during pregnancy on 82. Huynh HQ, deBruyn J, Guan L, et a. Probiotic preparation VSL#3 induces remission in children with mild to of periodontal disease: a preliminary randomized clinical trial. Journal of Oral Microbiology 2010, 2: 5344 - DOI: Gastroenterology. 2003;124(5):1202-9. Health. 2010 2010 Jul 8. atopic eczema in childhood—a meta-analysis. Br J Nutr. 2012;107:1–6. moderate acute ulcerative colitis: A pilot study. Inflamm Bowel Dis. 2009;15:760-8. 10.3402/jom.v2i0.5344 Mimura T, Rizzello F, Helwig U, et a. Once daily high dose probiotic therapy (VSL#3) for maintaining remission Weizman Z, Asli G, Alsheikh A. Effect of a probiotic infant formula on infections in child care centers: Comparison 71. Kalliomaki M, Salminen S, Arvilommi H, et al. Probiotics in primary prevention of atopic disease: a randomised 83. Miele E, Pascarella F, Giannetti E, et a. Effect of a probiotic preparation (VSL#3) on induction and maintenance of Twetman S et al. Short-term effect of chewing gums containing probiotic Lactobacillus reuteri on the levels in recurrent or refractory pouchitis. Gut. 2004;53:108-14. of two probiotic agents. Pediatrics 2005;115(1):5-9. placebo controlled trial. Lancet. 2001;357:1076–1079. remission in children with ulcerative colitis. Am J Gastroenterol. 2009;104:437-43. of inflammatory mediators in gingival crevicular fluid. Acta Odontol Scand. 67(1):19–24. Indrio F, Riezzo G, Raimondi F, et a. The effect of probiotics on feeding tolerance, bowel habits, and Abrahamsson TR, Jakobsson T, Bo¨ ttcher MF, et al. Probiotics in prevention of IgE associated eczema: a 72. Rautava S, Kalliomaki M, Isolauri E. Probiotics during pregnancy and breast-feeding might confer 84. Guandalini S, Magazzù G, Chiaro A, et al. VSL#3 improves symptoms in children with irritable bowel syndrom: A double-blind, randomized, placebo-controlled trial. J Allergy Clin Immunol 2007; 119: 1174–1180. Lonnermark E, Friman V, Lappas G, et a. Intake ofLactobacillus plantarumreduces certain gastrointestinal gastrointestinal motility in preterm newborns, a double-blind, placebo-controlled pilot study. J Pediatr. immunomodulatory protection against atopic disease in the infant. J Allergy Clin Immunol. 2002;109:119–121. multicenter, randomized, placebo-controlled, double-blind, crossover study. J Pediatr Gastroenterol Nutr. symptoms during treatment with antibiotics. J Clin Gastroenterol. 2010;44(2):106-12. 2008;152:801-6. 2012;51(1):24-30 Szajewska H, Mrukowicz JZ. Probiotics in the treatment and prevention of acute infectious diarrhea in infants and 73. Klarin B, Wullt M, et a. Lactobacillus plantarum299v reduces colonisation ofClostridium difficilein critically ill Indrio F, Riezzo G, et a. Lactobacillus reuteriaccelerates gastric emptying and improves regurgitation in infants. children: A systematic review of published randomized, double-blind, placebo-controlled trials. J Pediatr Kalliomaki M, Salminen S, Poussa T, et al. Probiotics and prevention of atopic disease: 4-year follow-up patients treated with antibiotics. Acta Anaesthesiologica Scandinavica. 2008;59:1096-102. Eur J Clin Invest. 2012;41(4):417-22. Gastroenterol Nutr. 2001;33(Suppl 2):S17-25. of a randomised placebo-controlled trial. Lancet. 2003;361:1869–1871. 85. Anukam K, Osazuwa E et al. 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95. Larsson P, Brandsborg E, Forsum U, et a. Extended antimicrobial treatment of bacterial vaginosis combined 105. Hickson M, D'Souza AL, Muthu N, et a. Use of probioticLactobacilluspreparation to prevent diarrhoea associated with humanLactobacillito find the best treatment and minimize the risk of relapses. BMC Infectious Diseases. with antibiotics: Randomised double blind placebo controlled trial. BMJ. 2007;335(7610):80. 2011;11:233. 106. Taipale T, Pienihakkinenen K, Isolauri E, et al.Bifidobacterium animalis subsp. lactis BB-12 in reducing the risk of 96. Oduyebo O, et a. The effects of antimicrobial therapy on bacterial vaginosis in non-pregnany women. Cochrane infections in infancy. Br J Nutr.2011;105:409-416. Collaboration. 2009:1-77. 107. Saavedra JM, Abi-Hanna A, Moore N, et al. Long-term consumption of infant formulas containing live probiotic 97. Agrawal A, Houghton LA, et a. Clinical trial: The effects of a fermented milk product containingBifidobacterium bacteria: tolerance and safety1-3. Am J Clin Nutr. 2004;79:261-7 lactisDN-173 010 on abdominal distension and gastrointestinal transit in irritable bowel syndrome with constipation. Alimentary Pharmacology & Therapeutics. 2008;29:104-1. 108. Corrêa NBO, Filho LAP, Penna FJ, et al. A Randomized Formula Controlled Trial of Bifidobacterium lactis and Streptococcus thermophiles for Prevention of Antibiotic-Associated Diarrhea in Infants. J Clin Gastroenterol. 2005;39(5):385-389. 98. Guyonnet D, Chassany O, Ducrotte P, et al. Effect of a fermented milk containingBifidobacterium animalisDN-173 010 on the health-related quality of life and symptoms in irritable bowel syndrome in adults in 109. Sheu B, Wu JJ, Lo CY, et a. Impact of supplement withLactobacillus-andBifidobacterium-containing yogurt on primary car: A multicenter, randomized, double-blind, controlled trial. Alimentary Pharmacology & triple therapy forHeliobacter pylorieradication. Alimentary Pharmacology & Therapeutics. 2002;16:1669-75. Therapeutics. 2007;1(263):475-86. 110. Sheu B, Cheng H, et a. Pretreatment withLactobacillus-andBifidobacterium-containing yogurt can improve the 99. Yang WX, Mei H, et a. Effect of a fermented milk containingBifidobacterium lactisDN-173010 on chinese efficacy if quadruple therapy in eradicating residualHeliobacter pyloriinfection after failed triple therapy. Am J Clin constipated women. World J Gastroenterol. 2008;14(40):6237-43. Nutr. 2006;83:864-9.

100. Merestein D, Murphy M, et a. Use of a fermented dairy probiotic drink containing lactobacillus casei (DN-114 111. Wang KY, Li SN, Liu CS, et a. Effects of ingestingLactobacillus-andBifidobacterium-containing yogurt in subjects 001) to decrease the rate of illness in kids: The DRINK study. A patient-oriented, double-blind, with colonizedHeliobacter pylori.. Am J Clin Nutr. 2004;80(3):737-41. cluster-randomized, placebo-controlled, clinical trial. Eur J Clin Nutr. 2010;64(7):669-77. 112. de Vrese M, Kristen H, Rautenberg P, Laue C, Schrezenmeir J. Probiotic lactobacilli and bifidobacteria in a 101. Pedone CA, Bernabeu AO, Postaire ER, et a. The effect of supplementation with milk fermented by fermented milk product with added fruit preparation Lactobacillus casei(strain DN-114 001) on acute diarrhoea in children attending day care centres. Int J Clin Pract. 1999;53(3):179-84. Beausoleil M, Fortier N, Guénette S, et a. Effect of a fermented milk combiningLactobacillus acidophilusCl1285 andLactobacillus caseiin the prevention of antibiotic-associated diarrhea: A randomized, double-blind, placebo-controlled trial . Can J Gastroentero. 2007;21(11):732-6.

Petricevic L, Witt A. The role ofLactobacillus casei rhamnosusLcr35 in restoring the normal vaginal flora after Sýkora J, Valecková K, Amlerová J, et a. Effects of a specially designed fermented milk product containing antibiotic treatment of bacterial vaginosis. BJOG. 2008;115(11):1369-74. probioticLactobacillus caseiDN-114 001 and the eradication ofH. pyloriin children: A prospective randomized double-blind study. J Clin Gastroenterol. 2005;39(8):692-8. Rossi A, Rossi T, Bertini M, et a. The use ofLactobacillus rhamnosusin the therapy of bacterial vaginosis. evaluation of clinical efficacy in a population of 40 women treated for 24 months. Arch Gynecol Obstet. Lin JS, Chiu YH, Lin NT, Chu CH, Huang KC, Liao KW, et al.Different effects of probiotic species/strains on Version 2014, (updated annually) SD-14-en 2010;281(6):1065-9. infections in preschool children: a double-blind,randomized, controlled study. Vaccine 2009;27(7):1073–9. Provided by an unrestricted educational grant from DANONE & Ferring Pharmaceuticals Larsson P, Brandsborg E, Forsum U, et a. Extended antimicrobial treatment of bacterial vaginosis combined Hickson M, D'Souza AL, Muthu N, et a. Use of probioticLactobacilluspreparation to prevent diarrhoea associated with humanLactobacillito find the best treatment and minimize the risk of relapses. BMC Infectious Diseases. with antibiotics: Randomised double blind placebo controlled trial. BMJ. 2007;335(7610):80. 2011;11:233. Taipale T, Pienihakkinenen K, Isolauri E, et al.Bifidobacterium animalis subsp. lactis BB-12 in reducing the risk of Oduyebo O, et a. The effects of antimicrobial therapy on bacterial vaginosis in non-pregnany women. Cochrane infections in infancy. Br J Nutr.2011;105:409-416. Collaboration. 2009:1-77. Saavedra JM, Abi-Hanna A, Moore N, et al. Long-term consumption of infant formulas containing live probiotic Agrawal A, Houghton LA, et a. Clinical trial: The effects of a fermented milk product containingBifidobacterium bacteria: tolerance and safety1-3. Am J Clin Nutr. 2004;79:261-7 lactisDN-173 010 on abdominal distension and gastrointestinal transit in irritable bowel syndrome with constipation. Alimentary Pharmacology & Therapeutics. 2008;29:104-1. Corrêa NBO, Filho LAP, Penna FJ, et al. A Randomized Formula Controlled Trial of Bifidobacterium lactis and Streptococcus thermophiles for Prevention of Antibiotic-Associated Diarrhea in Infants. J Clin Gastroenterol. 2005;39(5):385-389. Guyonnet D, Chassany O, Ducrotte P, et al. Effect of a fermented milk containingBifidobacterium animalisDN-173 010 on the health-related quality of life and symptoms in irritable bowel syndrome in adults in Sheu B, Wu JJ, Lo CY, et a. Impact of supplement withLactobacillus-andBifidobacterium-containing yogurt on primary car: A multicenter, randomized, double-blind, controlled trial. Alimentary Pharmacology & triple therapy forHeliobacter pylorieradication. Alimentary Pharmacology & Therapeutics. 2002;16:1669-75. Therapeutics. 2007;1(263):475-86. Sheu B, Cheng H, et a. Pretreatment withLactobacillus-andBifidobacterium-containing yogurt can improve the Yang WX, Mei H, et a. Effect of a fermented milk containingBifidobacterium lactisDN-173010 on chinese efficacy if quadruple therapy in eradicating residualHeliobacter pyloriinfection after failed triple therapy. Am J Clin constipated women. World J Gastroenterol. 2008;14(40):6237-43. Nutr. 2006;83:864-9.