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World J Gastroenterol. Mar 14, 2013; 19(10): 1527-1540
Published online Mar 14, 2013. doi: 10.3748/wjg.v19.i10.1527
Table 1 Results of clinical trials with probiotics in irritable bowel syndrome
Ref. Patients (n ) Duration of therapy Probiotic strains Dose (CFU/d) Outcomes Maupas et al [88 ] 34 1 mo Saccharomyces boulardii 9 × 109 Improved stool number and consistency Gade et al [89 ] 54 1 mo Paraghurt (Streptococcus faecium ) 1 × 10¹² Improved symptoms Halpern et al [90 ] 18 4 mo Lactobacillus acidophilus 2 × 1010 Improved symptoms O’Sullivan et al [91 ] 25 1 mo Lactobacillus GG 1 × 1010 No benefit Nobaek et al [92 ] 60 1 mo Lactobacillus plantarum 299V Pro-Viva® 5 × 107 Improved global symptoms Niedzielin et al [93 ] 40 1 mo Lactobacillus plantarum 299V Pro-Viva® 2 × 1010 Improved global symptoms Kim et al [94 ] 25 2 d-IBS VSL3® 9 × 10¹¹ Reduced bloating Tsuchiya et al [95 ] 68 3 mo Lactobacillus acidophilus 1.5 × 106 Improved symptoms Lactobacillus helveticus 1.3 × 109 Bifidobacterium 4.95 × 109 O’Mahony et al [96 ] 80 2 mo Bifidobacterium longum subspecies infantis vs Lactobacillus salivarius 1 × 1010 B. infantis : improved global symptoms and anti-inflammatory cytokine profileLactobacillus salivarius : no benefitKajander et al [97 ] 103 6 mo Mixture (2 strains of Lactobacillus rhamnosus , Bifidobacterium breve , Propionibacterium freudenreichii ) 8-9 × 109 Improved global symptoms Bittner et al [98 ] 25 0.5 mo 29 bacteria + prebiotic Prescript-Assist® 2.6 × 108 Improved wellbeing Sen et al [99 ] 12 1 mo Lactobacillus plantarum 299V Pro-Viva® 5 × 107 No benefit; Study design flawed Bausserman et al [100 ] 50 1.5 mo Lactobacillus GG 2 × 1010 No benefit Niv et al [101 ] 39 6 mo Lactobacillus GG 2 × 108 No benefit Francis severity IBS score Kim et al [102 ] 48 1 or 2 mo VSL3® 8 × 109 Reduced flatulence, retarded colonic transit Whorwell et al [103 ] 362 1 mo Bifidobacterium longum subspecies infantis 35 624 in 3 doses1 × 106 Improved global symptoms 1 × 108 1 × 1010 Long et al [104 ] 60 0.5 mo Bifidobacterium 2 × 108 Symptoms resolved Gawrońska et al [105 ] 104 1 mo Lactobacillus GG 6 × 109 Reduced frequency of pain Moon et al [106 ] 34 1 mo Bifidobacterium subtilis , Streptococcus faecium 750 mL/d, CFU/d not given Reduced frequency pain Marteau et al [107 ] 116 1 mo Lactibiane® (4 strains of Bifidobacterium longum , Lactobacillus acidophilus , Lactobacillus lactis , Streptococcus thermophilus ) 1 × 1010 Reduced painIncreased colonic transit in those with constipation Simrén et al [108 ] 76 1.5 mo Lactobacillus plantarum 299V 2 × 109 No benefit Simrén et al [109 ] 118 2 mo Lactobacillus paracasei ssp paracasei 2 × 1010 No benefit Guyonnet et al [110 ] 274 1.5 mo Bifidobacterium animalis , Streptococcus thermophilus and Lactobacillus bulgaricus 1.25 × 1010 1.2 × 109 Improved bloating and constipation Drouault-Holowacz et al [111 ] 116 1 mo Bifidobacterium longum , Lactobacillus acidophilus , Lactobacillus lactis , Streptococcus thermophilus 1 × 1010 Not significant in relieving symptoms Sinn et al [112 ] 40 1 mo Lactobacillus acidophilus 2 × 108 Improved abdominal pain and discomfort Enck et al [113 ] 297 1 mo Escherichia coli , Enterococcus faecalis 4.5 × 102 Improvement in pain Hun et al [114 ] 44 2 mo Bacillus coagulans 8 × 108 Improvement abdominal pain and bloating Dolin et al [115 ] 61 2 mo Bacillus coagulans 2 × 109 Diminution of diarrhea Ligaarden et al [116 ] 16 1 mo Lactobacillus plantarum 1010 /L Worsening of symptoms Moayyedi et al [117 ] 19 randomised controlled trials in 1650 patients Probiotics appear to be efficacious but the magnitude of benefit and the most effective strains are uncertain
Table 2 Results of clinical trials with probiotics in ulcerative colitis
Ref. Patients (n ) Duration of therapy Probiotic strains Dose (CFU/d) Outcomes Kruis et al [118 ] 120 12 wk Escherichia coli Nissle 191750 × 1010 Maintaining the remission (similar to 5-ASA) Rembacken et al [119 ] 116 1 yr Escherichia coli Nissle 19175 × 1010 Induction of remission (similar to 5-ASA); maintaining of relapses (similar to 5-ASA) Venturi et al [120 ] 20 1 yr VSL3® 5 × 10¹¹ Maintaining the remission Ishikawa et al [121 ] 21 1 yr Milk with bifidobacteria 10 × 108 Maintaining the remission Guslandi et al [122 ] 25 4 wk Saccharomyces boulardii 250 mg × 3 Induction of remission Kruis et al [123 ] 327 1 yr Escherichia coli Nissle 19172.5-25 × 109 Induction of remission (5-ASA better than probiotic) Tursi et al [124 ] 90 8 wk Balsalazide/VSL3® 900 × 108 Induction of remission Cui et al [125 ] 30 8 wk Bifidobacteria 1.26 g/d Maintaining of remission Kato et al [126 ] 20 12 wk Bifidobacterium -fermented milk vs placebo109 CDAI lower in Bifidobacterium fermented milk that in placebo Furrie et al [127 ] 18 4 wk Bifidobacterium longum + prebiotic (Synergy 1)4 × 10¹¹ Induction of remission Bibiloni et al [128 ] 32 6 wk VSL3® 1800 billion × 2 Induction of remission Zocco et al [129 ] 187 12 mo Lactobacillus GG vs mesalazina18 × 109 No difference between the treatment groups Henker et al [130 ] 34 12 mo Escherichia coli Nissle 19175 × 1010 Maintenance of remission Miele et al [131 ] 29 12 mo VSL3® 450-1800 × 109 Induction of remission (92.8% in treated with VSL3® and 36.4% in the placebo group) Sood et al [132 ] 147 12 wk VSL3® 3.6 × 10¹² Induction of remission (42.9% against 15.7% in the placebo group) Matthes et al [133 ] 57 4 wk Escherichia coli Nissle 191710-40 × 108 Induction of remission Sang et al [134 ] 13 RCTs Heterogenity between the studies in their methodology and results
Table 3 Results of clinical trials with probiotics in patients with Crohn’s disease
Ref. Patients (n) Duration of therapy Probiotic strains Dose (CFU/d) Outcomes Malchow et al [135 ] 24 3 mo Escherichia coli Nissle 19172.5 × 1010 Maintaining the remission Guslandi et al [136 ] 32 6 mo Saccharomyces boulardii 1 g Postsurgical prevention of CD recurrence (relapse rate probiotic+ 5-ASA vs 5-ASA alone) Prantera et al [137 ] 45 1 yr Lactobacillus GG 12 × 109 Postsurgical prevention of CD recurrence (no effects) Schultz al [138 ] 11 6 mo Lactobacillus GG 2 × 109 Probiotics are not superior to placebo in maintaining remission Bousvaros et al [139 ] 75 1 yr Lactobacillus GG 2 × 1010 Probiotics are not superior to placebo in maintaining remission Marteau et al [140 ] 98 6 mo Lactobacillus johnsonii 4 × 109 Postsurgical prevention of CD recurrence (recurrence rate decreased vs placebo) Chermesh et al [141 ] 30 24 mo Synbiotic 2000 (Pediococcus pentoseceus , Lactobacillus raffinolactis , Lactobacillus paracasi susp paracsei, Lactobacillusplantarum 2362 ) and 4 fermentable fibers vs placebo 10¹¹ Postsurgical prevention of CD recurrence (NS) Van Gossum et al [142 ] 70 12 wk Lactobacillus johnsonii or placebo1010 Postsurgical prevention of CD recurrence (NS) Rolfe et al [143 ] 7 RCTs No benefit of probiotics in the maintenance of remission of CD Rahimi et al [144 ] 8 RCTs None benefit for probiotic treatment in the maintenance of clinical remission of CD
Table 4 Reference studies concerning the probiotic role of bacterial DNA
Ref. Outcomes Lammers et al [23 ] Bacterial DNA from faeces collected after VSL-3 administration modulated a decrease of IL-1β and an increase of IL-10 Rachmilewitz et al [26 ] Study in a mouse IBD model: protective effects of probiotics contained in VSL-3 are mediated by their DNA and TLR9 signaling mediates anti-inflammatory effect Iliev et al [27 ] Lactobacillus rhamnosus GG DNA induces B-cell proliferation and activate DCGhadimi et al [28 ] Bacterial DNA inhibited IL-4 and IL-5 secretion in different Lactobacilli Ménard et al [30 ] Study from 5 bifidobacterial strains: unmethylated CpG motifs are specific to bacterial DNA by activating TLR9
Table 5 Reference studies concerning the probiotic role of molecules presented at the bacterial surface
Ref. Outcomes Mazmanian et al [33 ] Bacterial capsular PSA elaborated by Bacteroides fragilis activates CD4+ and elicits cytokine production Mazmanian et al [35 ] Purified PSA suppress pro-inflammatory IL-17 production and protects from inflammatory disease by induction of IL-10 Ryu et al [36 ] Purified LTA from Gram-positive bacteria has lower potency in the stimulation of Toll-like receptor-2 pathway to induce pro-inflammatory molecules. Grangette et al [37 ] Modified LTA is able to induce secretion of anti-inflammatory IL-10 Benz et al [39 ] Lipoproteins and glycoproteins at the cell surface are attractive candidates as probiotic molecules Schlee et al [40 ] Flagellins of the Escherichia coli Nissle 1917 induces expression of human β-defensin 2 Matsumoto et al [83 ] Purified PSPG-I from Lactobacillus casei Shirota has anti-inflammatory actions in chronic intestinal inflammatory disorders