Table 3.
Probiotics for IBD (Randomized trials)
| Author, year | Disease activity |
Case /Control |
Base Therapy | Agent (s) | Route | Therapy duration |
Outcomes, therapy vs control | PMID |
|---|---|---|---|---|---|---|---|---|
| Ulcerative colitis | ||||||||
| Kruis, 1997 | remission | 50/53 | Sterpod, salicylates | Escherichia coli Nissle1917 vs 5-ASA | oral | 12 w | Equivalent relapse rate to 5-ASA | 9354192 |
| Rembacken, 1999 | active | 57/59 | Steroid, pre-GEM | Escherichia coli Nissle1917 vs 5-ASA | oral | 3 m | Equivalent remission rate to 5-ASA | 10466665 |
| Rembacken, 1999 | remission | 44/39 | Steroid | Escherichia coli Nissle1917 vs 5-ASA | oral | 12 m | Equivalent remission rate to 5-ASA | 10466665 |
| Ishikawa, 2003 | remission | 11/10 | Steroid, sulfa | bifidobacteria-fermented milk | oral | 1 y | Improve relapse rate (27% vs 90%) | 12569115 |
| Cui, 2004 | remission | 15/15 | BIFICO (Enterococci, Bifidobacteria, Lactobacilli) | oral | 8 w | Improve ralapse rate (20% vs 93%) and cytokine profile | 15133865 | |
| Kruis, 2004 | remission | 162/165 | Escherichia coli Nissle1917 vs 5-ASA | oral | 12 m | Equivalent relapse rate to 5-ASA (36% vs 34%) | 15479682 | |
| Tursi, 2004 | active | 30/30/30 | 5-ASA | Low balsalazide + VSL#3 vs med balsalazide vs mesalazine | oral | 8 w | Improve remission rate (80% vs 77% vs 53%) | 15507864 |
| Kato, 2004 | active | 10/10 | Sulfa | bifidobacteria-fermented milk | oral | 12 w | Improve clinical, endoscopi and histological scores | 15569116 |
| Shanahan, 2006 | Lactobacillus salivarius UCC118 | NS | Abst (a) | |||||
| Zocco, 2006 | remission | 65/60/62 | LGG vs 5-ASA vs conbination | oral | 12 m | Improve relapse-free time (ralapse rate is similar) | 16696804 | |
| Miele, 2009 | active, newly diagnosed child | 14/15 | 5-ASA, steroid | VSL#3 | oral | 1 y | Improve remission rate (93% vs 36%), relapse rate (21% vs 73%) and endoscopic and histological scores | 19174792 |
| Fujimori, 2009 | inactive, mild | 40/40/40 | 5-ASA, steroid | Bifidobacterium longum vs Psyllium vs synbiotics | oral | 4 w | NS (synbiotics significantly improve remission rate) | 19201576 |
| Sood, 2009 | active | 77/70 | 5-ASA | VSL#3 | oral | 12 w | Improve remission rate (43% vs 16%) and clinical scores | 19631292 |
| Tursi, 2010 | active | 65/66 | 5-ASA, MNZ, AZA | VSL#3 | oral | 8 w | Improve clinical score (63% vs 41%) Remission rate (48% vs 32%, P=0.069) | 20517305 |
| Matthes, 2010 | active | 24/23/23/20 | Steroid | Escherichia coli Nissle1917 | rectal | 2w- | Dose-dependent benefit | 20398311 |
| Ng, 2010 | active | 14/14 | 5-ASA, AZA | VSL#3 | oral | 8 w | Improve DC cytokine profiles (↑IL-10, ↓IL-12p40) Clinical response (71% vs 36%, P=0.06) | 20155842 |
| Wildt, 2011 | remission | 20/12 | 5-ASA, salazopyrine | Probio-Tec (Lactobacillus acidophilus La-5, Bifidobacterium animalis subsp. lactis BB-12) | oral | 52 w | NS (relapse rate: 75% vs 92%) | 21453880 |
| D’Inca, 2011 | active | 8/11/7 | 5-ASA | Oral Lactobacillus casei DG + oral 5-ASA vs rectal Lactobacillus casei DG + oral 5-ASA vs oral 5-ASA | oral vs rectal | 8 w | TLR4, IL1b,microbiota: only rectal is effective. rectally administered L. casei DG, it modified colonic microbiota by increasing Lactobacillus spp. and reducing Enterobacteriaceae. | 20737210 |
| Oliva, 2012 | active, child | 16/15 | 5-ASA | Lactobacillus reuteri ATCC55730 | rectal | 8 w | Improve clinical and endoscopic Mayo scores, histological scores and cytokine profiles | 22150569 |
| Groeger, 2013 | active | 13/9 | Bifidobacterium infantis 35624 | oral | 6-8 w | Reduced CRP, TNF-a, IL-6 | 23842110 | |
| Petersen, 2014 | active | 25/25/25/25 | 5-ASA, AZA, 6-MP, steroid | +/− pre-cipro (1w) +/− E.coli Nissle1917 (7w) | oral | 7 w | NS | 24972748 |
| Yoshimatsu, 2015 | remission | 9/9 | 5-ASA, salazopyrin | Bio-three (Streptococcus faecalis T-110, Clostridium butyricum TO-A, Bificobacterium mesentericus TO-A) | oral | 12 m | Relapse: 0% vs 17%(3m), 9% vs 26%(6m), 22% vs 35%(9m) Remission: 70% vs 57% (12m) P=0.248 | 26019464 |
| Tamaki, 2016 | active | 28/28 | 5-ASA, AZA, steroid | Bificobacterium longum BB536 | oral | 8 w | Improve clinical and endoscopic scores | 26418574 |
| Palumbo, 2016 | active | 30/30 | 5-ASA | Lactobacillus salivarius, Lactobacillus acidophilus, Bifidobacterium bifidus BGN4 | oral | 24 m | Improve clinical and endoscopic scores | 27623957 |
| Matsuoka, 2018 | remission | 98/97 | 5-ASA | bifidobacteria-fermented milk | oral | 48 w | NS | 29450747 |
| Bharat, 2018 | active | 11/15/15/17 | SER-287 (cocktail of Firmicutes spores) placebo/placebo daily vs vanco/SER287 daily vs placebo/SER287 weekly vs vanco/SER-287 weekly | oral | 8 w | Improve remission rate (placebo/placebo daily: 0%, vanco/SER287 daily: 40%, placebo/SER287 weekly: 13.3%, vanco/SER-287 weekly: 17.7%) | Abst (b) | |
| Pouchitis | ||||||||
| Gionchetti, 2000 | remission | 20/20 | VSL#3 | oral | 9 m | Improve relapse rate (15% vs 100%) | 10930365 | |
| Gionchetti, 2003 | inactive | 20/20 | VSL#3 | oral | 12 m | Improve onset rate (10% vs 40%) and IBDQ | 12730861 | |
| Kuisma, 2003 | active | 10/10 | Lactobacillus rhamnosus GG | oral | 3 m | NS | 12622759 | |
| Mimura, 2004 | inactive | 20/16 | VSL#3 | oral | 12 m | Improve relapse rate (15% vs 94%) and IBDQ | 14684584 | |
| Tomasz, 2014 | active | 22/21 | Lactobacillus acidophilus, Lactobacillus delbrueckii supsp. bulgaricus, Bificobacterium bifidus | oral | 9m | Improve clinical and endoscopic scores and calprotectin | 24579075 | |
| Yasueda, 2016 | inactive | 9/8 | Clostridium butyricum MIYAIRI | oral | 24 m | Improve relapse rate (11% vs 50%) and CRP | 26510664 | |
| Bengtsson, 2016 | poor pouch function | 16/16 | Lactobacillus plantarum 299 + Bifidobacterium infantis Cure21 | oral | 21 d | NS | 27150635 | |
| Crohn’s disease | ||||||||
| Plein, 1993 | inactive | 10/7 | Saccharomyces boulardii | oral | 10 w | Improve CDAI (<150: 90% vs 14%) | 8465554 | |
| Malchow, 1997 | inactive | 16/12 | Steroid | Escherichia coli Nissle1917 | oral | 3 m | NS | 9451682 |
| Malchow, 1997 | active, inactive | 12/11 | Steroid | Escherichia coli Nissle1917 | oral | 12 m | NS (relapse rate: 33% vs 64%) | 9451682 |
| Guslandi, 2000 | remission | 16/16 | 5-ASA | Saccharomyces boulardii | oral | 6 m | Improve relapse rate (6% vs 38%) | 10961730 |
| Campieri, 2000 | remission | 20/20 | pre-rifaximin + VSL#3 vs 5-ASA | oral | 12 m | Improve endoscopic score (80% vs 60%) | Abst (c) | |
| Prantera, 2002 | remission | 23/22 | Lactobacillus casei subsp. rhamnosus | oral | 12 m | NS | 12171964 | |
| Schultz, 2004 | active | 5/6 | Steroid, antibiotics | Lactobacillus GG | oral | 6 m | NS | 15113451 |
| Bousvaros, 2005 | remission | 39/36 | 5-ASA, AZA, 6-MP, steroid | Lactobacillus GG | oral | 2 y | NS | 16116318 |
| Marteau, 2006 | inactive | 48/50 | Steroid | Lactobacillus johnsonii LA1 | oral | 6 m | NS | 16377775 |
| Van Gossum, 2007 | inactive | 34/36 | Lactobacillus johnsonii LA1 | oral | 3 m | NS | 17206696 | |
| Garcia Vilela, 2008 | inactive | 12/13 | 5-ASA, AZA, steroid, thalidomide. metronidazole | Saccharomyces boulardii | oral | 3 m | Improve intestinal permeability | 18584523 |
| Bourreille, 2013 | inactive | 59/66 | AZA, 6-MP, steroid, MTX, anti-TNF-α | Saccharomyces boulardii | oral | 1 y | NS | 23466709 |
| Fedorak, 2015 | inactive after surgery | 59/60 | VSL#3 | oral | 1 y | Improve mucosal inflammatory cytokine levels Reccurence of lesions (10% vs 27%, P=0.09) | 25460016 | |
IBD: inflammatory bowel disease, PMID: PubMed identifier, NS: no statistically significant difference in disease activity, 5-ASA: 5-aminosalicylic acid, sulfa: salazosulfapyridine, AZA; azathioprine, 6-MP: 6-Mercaptopurine, MTX: methotrexate, DC: dendritic cell, TLR: toll-like receptor, IBDQ: inflammatory bowel disease questionnaire, CDAI: Crohn’s disease activity index,VSL#3: Lactobacillus casei, L. plantarum, L. acidophilus, L. delbrueckii subsp. bulgaricus, Bifidobacterium longum, B. breve, B. infantis, Streptococcus salivarius subsp. thermophilus, bifidobacteria-fermented milk containing Bifidobacterium breve Yakult, Bifidobacterium bifidum Yakult, Lactobacillus acidophillus YIT0168, ↑:increase, ↓:decrease. Abst (a): Gastroenterology 2006, 130, A44, Abst (b): Gastroenterology 2018, 154, S85, Abst (c): Gastroenterology 2000, 118, A781.