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©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. May 7, 2008; 14(17): 2650-2661
Published online May 7, 2008. doi: 10.3748/wjg.14.2650
Table 1 Description of 20 randomized, controlled trials of probiotics for IBS included in systematic review
Reference Probiotic Type of control Number of subjects randomized Number analyzed Dose (cfu/d) Duration of treatment (wk) % attrition Maupas[45 ] Saccharomyces cerevisiae boulardii lyo Placebo capsules 34 34 9 × 109 4 0 Gade[46 ] Streptococcus faecium 40371 Placebo tablets 58 54 1 × 1012 4 7 Halpern[47 ] L. acidophilus (heat killed) “Lacteol Fort”Placebo capsules 29 18 2 × 1010 6 38 Nobaek[48 ] Lactobacillus plantarum DSM9843, in rose hip drinkPlacebo plain rose hip drink 60 52 5 × 107 4 13 O'Sullivan[49 ] Lactobacillus rhamnosus GG Placebo tablets 24 19 1 × 1010 8 21 Niedzielin[50 ] Lactobacillus plantarum 299v, “ProViva” drinkPlacebo drink 40 40 2 × 1010 4 0 Kim[51 ] VSL#3 (mix of 8 strains) powder packet1 Placebo powder 25 25 9 × 1011 8 4 Bausserman[52 ] Lactobacillus rhamnosus GG Placebo capsules 58 50 2 × 1010 6 22 Bittner[53 ] Prescript-assist® 29 soil strains and prebiotic “leonardite” Placebo capsules 27 25 2.6 × 108 2 7 Kajander[54 ] L. rhamnosus GG + L. rham. LC705 + Bifido. breve Bb99 +Prop. freudenreichii Placebo capsules 103 81 8-9 × 109 24 21 Kim[55 ] VSL#3 yogurt1 Placebo yogurt 48 48 8 × 109 4 0 Niv[56 ] Lactobacillus reuteri 55730 Placebo capsules 54 39 2 × 108 24 28 O’Mahony[17 ] L. salivaricus UCC4331 Placebo drink 54 51 1 × 1010 8 16 O’Mahony[17 ] Bifido. infantis 35624 Placebo drink 53 49 1 × 1010 8 16 Kim[57 ] B. subtilus + Strept. faecalis Placebo capsules 40 34 3 × 1010 4 15 Simren[58 ] L. plantarum 299v in rose hip drinkplain rose hip drink 66 58 2 × 109 6 12 Whorwell[35 ] Bifido. infantis 35624 in 3 dosesPlacebo capsules 362 292 1 × 106 4 19 1 × 108 1 × 1010 Enck[59 ] E. coli + Strept faecalis drink Placebo drink 297 264 4.5 × 102 8 11 Gawronska[60 ] L. rhamnosus GG Placebo capsules 37 37 6 × 109 4 0 Marteau[61 ] Bifido. longum, Lact acidophilus, Lactococcus lactis, Strept. thermophilus Placebo capsules 106 100 1 × 1010 4 6 Simren[62 ] Lact. paracasei, Lact acidophilus, Bifido. lactis in yoghurtControl milk 74 67 2 × 1010 8 9
Table 2 Examples of excluded randomized, controlled trials of probiotics for IBS
Reference Probiotic Number of subjects randomized Number of subjects analyzed Dose (cfu/mL) Duration Exclusion reason DiBaise[63 ] L. plantarum 299v vs placebo29 20 6 × 109 4 wk Withdrawn by author Saggioro[64 ] L. plantarum + L. acidophilus 46 39 1 × 1011 4 wk Quality score = 2.0 Saggioro[64 ] L. plantarum + Bifido. breve 44 37 1 × 1010 4 wk Quality score = 2.0 Long[65 ] Bifido. (species not given) 60 60 6 × 109 2 wk Quality score = 2.5 Kajander[66 ] L. rhamnosus GG + L. rham. LC705 + Bifid. breve Bb99 +Prop. freudenreichii 103 83 8-9 × 109 6 mo Duplicate study of Kajander K 2005 Bittner[67 ] Prescript-assist® , 29 soil strains and prebiotic 24 24 2.6 × 108 Varied Controls from Bittner 2005 study, phase 4 study Moon[68 ] Bacillus subtilis + St. faecium 34 34 750 mL/d, cfu/d not given 4 wk Outcome data not provided for each group in abstract
Table 3 Quality scoring for 20 randomized, controlled trials of probiotics for IBS (Linde Internal Validity Scale)
Reference Total quality score1 Treatment allocation Randomization method Baseline comparison Patients blinded Evaluators blinded Handling and reporting of withdrawals/use of ITT Data source2 Maupas[45 ] 6 1 1 1 1 1 1 Paper Gade[46 ] 4.5 1 1 0 1 1 0.5 Paper Halpern[47 ] 4 1 1 0.5 1 0.5 0 Paper Nobaek[48 ] 3 1 0 0 1 0.5 0.5 Paper O'Sullivan[49 ] 3 1 0 1 0.5 0.5 0 Author Niedzielin[50 ] 4 1 0 1 1 0 1 Paper Kim[51 ] 4.5 1 0 0.5 1 1 1 Paper Bausserman[52 ] 5.5 1 1 1 1 1 0.5 Paper Bittner[53 ] 3 1 0 0 0.5 0.5 1 Author Kajander[54 ] 4.5 1 1 1 0.5 0.5 0 Paper Kim[55 ] 4 1 0 1 1 0.5 0.5 Paper Niv[56 ] 3.5 1 0 0.5 1 0.5 0.5 Paper O’Mahony[17 ] 4.5 1 1 0 1 1 0.5 Paper Kim[57 ] 4 1 0 1 0.5 0.5 1 Paper Simren[58 ]3 3 1 0.5 0 1 0.5 0 Author Whorwell[35 ] 3.5 1 0 0.5 1 0.5 0.5 Paper Enck[59 ]3 4 1 0.5 0 1 0.5 1 Author Gawronska[60 ] 4.5 1 1 0 1 0.5 1 Paper Marteau[61 ]3 4.5 1 0.5 1 1 0.5 0.5 Author Simren[62 ]3 3.5 1 0.5 0 1 0 1 Author
Table 4 Outcome assessment and reporting for 20 included clinical trials of probiotics for IBS
Outcome Reference Global response Abdominal pain Bloating/distension Flatulence Stool frequency Mucous Stool consistency Dyspepsia Maupas[45 ] R R R R R R Gade[46 ] R R R R R Halpern[47 ] R A A A A A Nobaek[48 ] R R R A R O’Sullivan[49 ] R R A R A Niedzielin[50 ] R R R A A Kim[51 ] R R R R R R Bausserman[52 ] A R R A A Bittner[53 ] A A A Kajander[54 ] R R R R R A A Kim[55 ] R R R R R Niv[56 ] R R R A O’Mahony[17 ] R R R A R Kim[57 ] R A A A A Simren[58 ] R A A A A A A Whorwell[35 ] R R R R A Enck[59 ] R R A A A Gawronska[60 ] R Marteau[61 ] R R A A Simren[62 ] R A A Percent reporting 65% 80% 50% 40% 25% 0 30% 5%
Table 5 Global Improvement in IBS Symptoms in 14 probiotic/placebo treatment arms
Reference Probiotic Global improvement in IBS symptoms Definition of primary outcome1 Probiotic n /n (%) Placebo n /n (%) Maupas[45 ] Saccharomyces cerevisiae boulardii lyo 13/16 (81) 13/18 (72) Improvement of symptoms Gade[46 ] Strept faecalis 26/32 (81) 9/22 (41) Improvement of symptoms based on physician assessment Halpern[47 ] L. acidophilus 17/18 (94) 13/18 (72) Absence of symptoms Nobaek[48 ] L. plantarum 11/25 (44) 7/27 (26) Decrease ≥ 1.5 on VAS symptom scale Niedzielin[50 ] L. plantarum 9/20 (45) 3/20 (15) Absence of symptoms Kim[51 ] VSL#32 4/12 (34) 5/13 (38) Satisfactory relief of IBS symptoms Kajander[54 ] L. rhamnosus GG + L. rham. LC705 + Bifid. breve Bb99 + Prop. freudenreichii 31/41 (76) 17/40 (43) Symptoms alleviated based on significant reduction of symptom scores Simren[58 ] L. plantarum 10/29 (35) 11/29 (38) Reduction ≥ 50% of total symptom score Whorwell[35 ] Bifido. infantis (dose, 106 cfu/mL)33/74 (44) 32/76 (42) Adequate relief of symptoms Whorwell[35 ] Bifido. infantis (dose, 108 cfu/mL)45/72 (62) 32/76 (42) Adequate relief of symptoms Whorwell[35 ] Bifido. infantis (dose, 1010 cfu/mL)26/71 (37) 32/76 (42) Adequate relief of symptoms Enck[59 ] E. coli + Strept faecalis 102/149 (68) 56/148 (38) Reduction of ≥ 50% in total symptom score Marteau[61 ] Bifido. longum, L. acidophilus, Lactococcus lactis, Strept thermophilus 20/47 (42.6) 22/52 (42.3) Relief of discomfort Simren[62 ] L. paracasei, L. acidophilus, Bifido. lactis in yoghurt 14/33 (42) 17/34 (50) Reduction of ≥ 50% in total symptom score
Table 6 Relief of abdominal pain in 11 probiotic/placebo treatment arms
Reference Probiotic Improvement in abdominal pain Definition of secondary outcome1 Probiotic n /n (%) Placebo n /n (%) Gade[46 ] Strept faecalis 25/32 (78) 10/22 (45) Absence or presence of symptom Nobaek[48 ] L. plantarum 9/25 (36) 5/27 (18) Decrease ≥ 1.5 on VAS symptom scale O'Sullivan[49 ] L. rhamnosus GG 9/19 (47) 12/19 (63) Symptom improved Niedzielin[50 ] Lacto plantarum 20/20 (100) 11/20 (55) Absence of symptoms Bausserman[52 ] Lacto rhamnosus GG 11/25 (44) 10/25 (40) Decrease of ≥ 1 point symptom score Kajander[54 ] L. rhamnosus GG + L. rham. LC705 + Bifid. breve Bb99 +Prop. freudenreichii 27/41 (66) 17/40 (43) Symptoms alleviated Whorwell[35 ] Bifido. infantis (106 dose)32/74 (43) 39/76 (52) Adequate relief of symptoms Whorwell[35 ] Bifido. infantis (108 dose)42/72 (59) 39/76 (52) Adequate relief of symptoms Whorwell[35 ] Bifido. infantis (1010 dose)28/71 (39) 39/76 (52) Adequate relief of symptoms Enck[59 ] E. coli + Strept faecalis 108/149 (72) 66/148 (45) ≥ 50% decrease in symptom score Gawronska[60 ] Lacto rhamnosus GG 6/18 (33) 1/19 (5) Absence of pain
Table 7 Recommendations for future research studies examining probiotics as a treatment for irritable bowel syndrome
Recommendations More trials testing the same probiotic strain Larger sample size Longer duration of treatment and follow-up Intention to treat analysis: All participants analyzed with the group to which they were originally assigned, regardless of compliance with treatment, response to treatment, or use of prohibited (non-study) medications. Greater efforts to minimize loss to follow-up Standardized assessment of IBS outcomes Provide some assessment of global relief of IBS symptoms Detailed collection and reporting of data on potential adverse reactions