Table 1: Summary of randomized clinical intervention trials of probiotics in IBD.

ReferenceType of studyNumber of patientsAge of patients (years)Characteristics of patientsProbiotic strainMedicationIntervention time/doseForm of administrationMain outcome

Crohn’s disease (CD) Prantera et al., 2002 [50]RDBPCT4522–71Patients with a complete resection of all diseased intestineLactobacillus rhamnosus GGNo365 d/6 1010 CFU twice dailyOral No effects compared with placebo group
Schultz et al., 2004 [51]RDBPCT11Patients with moderate to active CDLactobacillus rhamnosus GGYes183 d/2 109 CFU per dayOralNo effects compared with placebo group
Bousvaros et al., 2005 [52]RDBPCT755–21Patients on CD remissionLactobacillus rhamnosus GG Yes730 d/1 1010 CFU twice dailyOralNo effects compared with placebo group
Marteau et al., 2006 [53]RDBPCT9827–42Patients that had undergone surgical resectionLactobacillus. johnsonii LA1Yes183 d/2 109 CFU twice daily OralNo effects compared with placebo group
van Gossum et al., 2007 [54]RDBPCT7018–65Patients with an elective ileocaecal resectionLactobacillus johnsonii LA1No84 d/1 1010 CFU per dayOralNo effects compared with placebo group
Chermesh et al., 2007 [56]RDBPCT3025 (mean age)Patients that had undergone surgery treatment*Synbiotic 2000Yes730 d/1 1010 CFU per dayOralNo effects compared with placebo group
Fujimori et al., 2007 [55]CS1027 (mean age)Patients with active CD*Synbiotic therapyYes395 d/7.5 1010 CFU per day and 3.3 g of psyllium thrice dailyOralSynbiotic therapy was safely and effectively used to treat active CD
Steed et al., 2010 [57]RDBPCT3518–79Patients with active CDBifidobacterium longum plus *Synergy 1Yes183 d/2 1011 viable CFU and 6 g Synergy I twice dailyOralSynbiotic improved clinical symptoms in patients with active CD

Ulcerative colitis (UC)Ishikawa et al., 2003 [60]RCT2139–60Patients on UC remission *BFMYes365 d/1 1010 CFU per dayOralBFM supplementation successfully maintained remission
Kato et al., 2004 [62]RPCT2032 (mean age)Patients with active UC*BFMYes84 d/1 1010 CFU per dayOralBFM supplementation was more effective than conventional treatment alone
Tursi et al., 2004 [75]RCT9019–69Newly diagnosed or recently relapsed mild to moderate UC*VSL#3Yes56 d/3 1011 CFU per dayOralBalsalazide/VSL#3 was significantly superior to balsalazide alone and to mesalazine in obtaining remission
Cui et al., 2004 [65]RCT30Patients with active UC*BIFICOYes56 d/1.26 g per dayOralBIFICO administration impeded the activation of NF-B and elevated the expression of IL-10
Furrie et al., 2005 [71]RCT1824–67Patients with active UCBifidobacterium longum plus *Synergy 1Yes28 d/2 1011 CFU and 6 g of Synergy 1 twice dailyOralShort-term treatment improved the full clinical appearance of chronic inflammation in patients with active UC
Zocco et al., 2006 [67]ROLT18733 (mean age)Patients on UC clinical remissionLactobacillus. GGYes365 d/6 109 CFU twice dailyOralLactobacillus  GG was not inferior to mesalazine and was significantly better at delaying relapses
Fujimori et al., 2009 [72]RCT120Patients on remission or with mildly active UC without a history of operation for UCBifidobacterium longum plus psylliumYes28 d/2 109 CFU per day and 4 g of psyllium twice dailyOralSynbiotic treatment improved the quality of life better than probiotic or prebiotic treatment
Miele et al., 2009 [23]RDBPCT291.7–16.1Children newly diagnosed with UC*VSL#3Yes365 d/4.5 1011–1.8 1012 CFU per dayOralVSL#3 was safe and effective in children treated for active UC**
Hegazy and El-Bedewy, 2010 [68]RCT4547 (mean age)Mild to moderate UC patients with chronic diarrhea*LacteolYes56 d/1 1010 CFU per dayOralSupplementation with probiotics could be advantageous in preventing relapse of UC and maintaining remission
Tursi et al., 2010 [61]RDBPCT13147 (mean age)Patients with mild to moderate relapsing UC*VSL#3Yes56 d/1.8 1012 CFU twice dailyOralVSL#3 administration reduced the UCDAI scores in patients affected by relapsing mild-to-moderate UC
D’Incà et al., 2011 [70]RCT26Patients with mild left-side UCLactobacillus casei DGYes56 d/8 108 CFU twice dailyOral and rectal5-ASA plus rectally administered probiotic modified the colonic microbiota, reduced the expression of TLR-4,  IL-1β, and increased IL-10 mRNA
Wildt et al., 2011 [64]RDBPCT32≥18Patients with UC in remission*Probio-Tec AB-25No364 d/2.5 1010 CFU per dayOralProbio-Tec AB-25 was well tolerated
Ishikawa et al., 2011 [73]RCT4145.5 (mean age)Patients with mild to moderate UCBifidobacterium breve strain Yakult plus GOSYes365 d/1 109 CFU thrice a day and 5.5 g of GOS once a dayOralSynbiotic administration can improve the clinical condition
Oliva et al., 2012 [69]RCT317–18Patients with mild to moderate UCLactobacillus reuteris ATCC 55730Yes61 d/1 1010 CFU per dayRectal enemaRectal infusion decreased the expression of proinflammatory cytokines and increased the expression of IL-10 in children

5-ASA: 5-aminosalicylic acid; BFM: bifidobacteria-fermented milk; CFU: colonic forming unit; CS: clinical study; d: days; GOS: galactooligosaccharide; IBS: irritable bowel syndrome; IL: interleukin; NF-κB: nuclear factor kappa B; OPUM: open-label prospective uncontrolled multicenter study; RCT: randomized clinical trial; RDBPCT: randomized double-blind placebo-controlled trial; ROLT: randomized open-label trial; RPCT: randomized placebo-controlled trial, TLR: toll-like receptor; UCDAI: ulcerative colitis disease activity index.
*Description of the bacterial and prebiotic contents of each product Synbiotic 2000: Pediococcus pentosaceus, L. raffinolactis, L. paracasei subsp. paracasei 19, and L. plantarum 2362 (1010 CFU of each bacteria) and -glucans, inulin, pectin, and resistant starch (2.5 g of each fermentable fiber). Synbiotic therapy: Bifidobacterium breve and Lactobacillus casei (3 1010 CFU/daily of each bacteria) and 1.5 1010 CFU/daily of Bifidobacterium longum plus 3.3 g of psyllium twice daily. Synergy I: Orafti, Tienen, Belgium. BFM: live Yakult strains of Bifidobacterium breve, Bifidobacterium bifidum, and Lactobacillus acidophilus YIT 0168 in at least 109 per 100 mL bottle. VSL#3: Lactobacillus casei, Lactobacillus plantarum, Lactobacillus acidophilus and Lactobacillus delbrueckii subsp. bulgaricus, Bifidobacterium longum, Bifidobacterium breve, Bifidobacterium infantis, Streptococcus salivarius subsp. thermophilus, and cornstarch. BIFICO: bifid triple viable capsule (oral capsules of live enterococci, bifidobacteria, and lactobacilli). Lacteol: 1 1010 CFU of Lactobacillus delbrueckii and Lactobacillus fermentum. Probio-Tec AB 25: Lactobacillus acidophilus strain LA-5 and Bifidobacterium animalis subsp. lactis strain BB-12 (1.25 1010 of each bacteria). Synbiotic zir fos: Bifidobacterium longum W11 (5 109 CFU) and Fos-Actilight (2.5 g). **Relative Risk of relapse within 1 year of follow-up (RR: 0.32 CI: 0.025–0.773).