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Copyright ©2008 The WJG Press and Baishideng.
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
ReferenceProbioticType of controlNumber of subjects randomizedNumber analyzedDose (cfu/d)Duration of treatment (wk)% attrition
Maupas[45]Saccharomyces cerevisiae boulardii lyoPlacebo capsules34349 × 10940
Gade[46]Streptococcus faecium 40371Placebo tablets58541 × 101247
Halpern[47]L. acidophilus (heat killed)“Lacteol Fort”Placebo capsules29182 × 1010638
Nobaek[48]Lactobacillus plantarum DSM9843, in rose hip drinkPlacebo plain rose hip drink60525 × 107413
O'Sullivan[49]Lactobacillus rhamnosus GGPlacebo tablets24191 × 1010821
Niedzielin[50]Lactobacillus plantarum 299v, “ProViva” drinkPlacebo drink40402 × 101040
Kim[51]VSL#3 (mix of 8 strains) powder packet1Placebo powder25259 × 101184
Bausserman[52]Lactobacillus rhamnosus GGPlacebo capsules58502 × 1010622
Bittner[53]Prescript-assist® 29 soil strains and prebiotic “leonardite”Placebo capsules27252.6 × 10827
Kajander[54]L. rhamnosus GG + L. rham. LC705 + Bifido. breve Bb99 +Prop. freudenreichiiPlacebo capsules103818-9 × 1092421
Kim[55]VSL#3 yogurt1Placebo yogurt48488 × 10940
Niv[56]Lactobacillus reuteri 55730Placebo capsules54392 × 1082428
O’Mahony[17]L. salivaricus UCC4331Placebo drink54511 × 1010816
O’Mahony[17]Bifido. infantis 35624Placebo drink53491 × 1010816
Kim[57]B. subtilus + Strept. faecalisPlacebo capsules40343 × 1010415
Simren[58]L. plantarum 299v in rose hip drinkplain rose hip drink66582 × 109612
Whorwell[35]Bifido. infantis 35624 in 3 dosesPlacebo capsules3622921 × 106419
1 × 108
1 × 1010
Enck[59]E. coli + Strept faecalis drinkPlacebo drink2972644.5 × 102811
Gawronska[60]L. rhamnosus GGPlacebo capsules37376 × 10940
Marteau[61]Bifido. longum, Lact acidophilus, Lactococcus lactis, Strept. thermophilusPlacebo capsules1061001 × 101046
Simren[62]Lact. paracasei, Lact acidophilus, Bifido. lactis in yoghurtControl milk74672 × 101089
Table 2 Examples of excluded randomized, controlled trials of probiotics for IBS
ReferenceProbioticNumber of subjects randomizedNumber of subjects analyzedDose (cfu/mL)DurationExclusion reason
DiBaise[63]L. plantarum 299v vs placebo29206 × 1094 wkWithdrawn by author
Saggioro[64]L. plantarum + L. acidophilus46391 × 10114 wkQuality score = 2.0
Saggioro[64]L. plantarum + Bifido. breve44371 × 10104 wkQuality score = 2.0
Long[65]Bifido. (species not given)60606 × 1092 wkQuality score = 2.5
Kajander[66]L. rhamnosus GG + L. rham. LC705 + Bifid. breve Bb99 +Prop. freudenreichii103838-9 × 1096 moDuplicate study of Kajander K 2005
Bittner[67]Prescript-assist®, 29 soil strains and prebiotic24242.6 × 108VariedControls from Bittner 2005 study, phase 4 study
Moon[68]Bacillus subtilis + St. faecium3434750 mL/d, cfu/d not given4 wkOutcome 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)
ReferenceTotal quality score1Treatment allocationRandomization methodBaseline comparisonPatients blindedEvaluators blindedHandling and reporting of withdrawals/use of ITTData source2
Maupas[45]6111111Paper
Gade[46]4.5110110.5Paper
Halpern[47]4110.510.50Paper
Nobaek[48]310010.50.5Paper
O'Sullivan[49]31010.50.50Author
Niedzielin[50]4101101Paper
Kim[51]4.5100.5111Paper
Bausserman[52]5.5111110.5Paper
Bittner[53]31000.50.51Author
Kajander[54]4.51110.50.50Paper
Kim[55]410110.50.5Paper
Niv[56]3.5100.510.50.5Paper
O’Mahony[17]4.5110110.5Paper
Kim[57]41010.50.51Paper
Simren[58]3310.5010.50Author
Whorwell[35]3.5100.510.50.5Paper
Enck[59]3410.5010.51Author
Gawronska[60]4.511010.51Paper
Marteau[61]34.510.5110.50.5Author
Simren[62]33.510.50101Author
Table 4 Outcome assessment and reporting for 20 included clinical trials of probiotics for IBS
Outcome
ReferenceGlobal responseAbdominal painBloating/distensionFlatulenceStool frequencyMucousStool consistencyDyspepsia
Maupas[45]RRRRRR
Gade[46]RRRRR
Halpern[47]RAAAAA
Nobaek[48]RRRAR
O’Sullivan[49]RRARA
Niedzielin[50]RRRAA
Kim[51]RRRRRR
Bausserman[52]ARRAA
Bittner[53]AAA
Kajander[54]RRRRRAA
Kim[55]RRRRR
Niv[56]RRRA
O’Mahony[17]RRRAR
Kim[57]RAAAA
Simren[58]RAAAAAA
Whorwell[35]RRRRA
Enck[59]RRAAA
Gawronska[60]R
Marteau[61]RRAA
Simren[62]RAA
Percent reporting65%80%50%40%25%030%5%
Table 5 Global Improvement in IBS Symptoms in 14 probiotic/placebo treatment arms
ReferenceProbioticGlobal improvement in IBS symptoms
Definition of primary outcome1
Probiotic n/n (%)Placebo n/n (%)
Maupas[45]Saccharomyces cerevisiae boulardii lyo13/16 (81)13/18 (72)Improvement of symptoms
Gade[46]Strept faecalis26/32 (81)9/22 (41)Improvement of symptoms based on physician assessment
Halpern[47]L. acidophilus17/18 (94)13/18 (72)Absence of symptoms
Nobaek[48]L. plantarum11/25 (44)7/27 (26)Decrease ≥ 1.5 on VAS symptom scale
Niedzielin[50]L. plantarum9/20 (45)3/20 (15)Absence of symptoms
Kim[51]VSL#324/12 (34)5/13 (38)Satisfactory relief of IBS symptoms
Kajander[54]L. rhamnosus GG + L. rham. LC705 + Bifid. breve Bb99 + Prop. freudenreichii31/41 (76)17/40 (43)Symptoms alleviated based on significant reduction of symptom scores
Simren[58]L. plantarum10/29 (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 faecalis102/149 (68)56/148 (38)Reduction of ≥ 50% in total symptom score
Marteau[61]Bifido. longum, L. acidophilus, Lactococcus lactis, Strept thermophilus20/47 (42.6)22/52 (42.3)Relief of discomfort
Simren[62]L. paracasei, L. acidophilus, Bifido. lactis in yoghurt14/33 (42)17/34 (50)Reduction of ≥ 50% in total symptom score
Table 6 Relief of abdominal pain in 11 probiotic/placebo treatment arms
ReferenceProbioticImprovement in abdominal pain
Definition of secondary outcome1
Probiotic n/n (%)Placebo n/n (%)
Gade[46]Strept faecalis25/32 (78)10/22 (45)Absence or presence of symptom
Nobaek[48]L. plantarum9/25 (36)5/27 (18)Decrease ≥ 1.5 on VAS symptom scale
O'Sullivan[49]L. rhamnosus GG9/19 (47)12/19 (63)Symptom improved
Niedzielin[50]Lacto plantarum20/20 (100)11/20 (55)Absence of symptoms
Bausserman[52]Lacto rhamnosus GG11/25 (44)10/25 (40)Decrease of ≥ 1 point symptom score
Kajander[54]L. rhamnosus GG + L. rham. LC705 + Bifid. breve Bb99 +Prop. freudenreichii27/41 (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 faecalis108/149 (72)66/148 (45)≥ 50% decrease in symptom score
Gawronska[60]Lacto rhamnosus GG6/18 (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