Table 1.
List of controlled clinical trials on adverse effects of probiotics versus placebo in inflammatory bowel disease.
| Author, Year and Country | IBD Type | Intervention | No. of Patients | Dose and Duration | Side Effects | Study Design |
|---|---|---|---|---|---|---|
| Prantera et al., 2002 Italy [32] |
CD | Lactobacillus GG | 45 | 12 billion CFU/day for 52 weeks |
Not described | DB, RCT |
| Ishikawa et al., 2003 Japan [33] |
UC | Bifidobacteria-fermented milk (B. breve, and B. bifidum, and L. acidophilus YIT 0168 Yakult) | 21 | at least 10 billion per 100 mL bottle for 1 year |
Coryza, Abdominal pain |
RCT |
| Kato et al., 2004 Japan [27] |
UC | B. bifidum + B. breve Yakult + L. acidophillus | 20 | 10 billion per 100 mL/day for 12 weeks |
No side effects in both arms |
RCT |
| Furrie et al., 2005 UK [28] | UC | B. longum + Synergy | 18 | 2 × 1011 CFU twice daily + 6 g fructo-oligosaccharide/inulin for 4 weeks. |
No side effects in both arms |
DB, RCT |
| Marteau et al., 2006 France [34] |
CD | L. johnsonii LA1 | 98 | 2 × 109 CFU 2packets/day for 6 months |
Digestive disorders | DB, RCT |
| Sood et al., 2009 North India [35] | UC | VSL#3 | 147 | 3600 billion CFU/day for 12 weeks |
Abdominal pain, Unpleasant taste |
MC, DB, RCT |
| Matthes et al., 2010 Germany [36] |
UC | E. coli Nissle 1917 | 90 | 108 viable EcN/mL in 40, or 20 or 10 mL enemas/day for at least 2 weeks |
Gastrointestinal disorders, Flatulence |
Explorative, MC, DB, RCT |
| Steed et al., 2010 UK [15] | CD | B. longum + Synergy | 35 | 2 × 1011 CFU twice daily + 6 g fructo-oligosaccharide/inulin for 6 months |
Not better specified (2 patients unable to tolerate synbiotic) |
DB, RCT |
| Tursi et al., 2010 Italy [12] |
UC | VSL#3(L. paracasei, L. plantarum, L. acidophilus, and L. delbrueckii subsp bulgaricus B. longum, B. breve, and B. infantis, Streptococcus thermophilus) | 144 | 3600 billion CFU/day for 8 weeks |
Abdominal bloating and discomfort, Unpleasant taste, Dizziness, Flu-like symptoms |
MC *, DB #, RCT † |
| Wildt et al., 2011 Denmark [30] | UC | L. acidophilus LA-5 + B. animalis subsp. lactis BB-12 | 32 | 1.5 × 1011 CFU/day for 52 weeks |
Gastrointestinal symptoms equally reported in both arms |
DB, RCT |
| Ishikawa et al., 2011 Japan [29] | UC | B. breve Yakult + GOS | 41 | 109 CFU/g three times daily + 5.5 g of galacto-oligosaccharide once a day for 1 year |
diarrhea or abdominal pain. (without given number) |
RCT |
| Yoshimatsu et al., 2015 Japan [31] | UC | 1 tablet = Streptococcus faecalis T-110 (2 mg) + Clostridium butyricum TO-A (10 mg) + Bacillus mesentericus TO-A (10 mg) | 60 | 9 tablets daily for 1 year |
No side effects in both arms |
DB, RCT |
| Tamaki et al., 2016 Japan [37] | UC | B. longum 536 | 56 | 2.3 × 1011 three times daily for 8 weeks |
Dry cough | MC, DB, RCT |
| Matsuoka et al., 2018 Japan [38] | UC | B. breve Yakult (10 × 109) + L. acidophilus (109) | 195 | 11 billion/day for 48 weeks |
Body odor, Abdominal bloating, Stress |
MC, DB, RCT |
* multicenter trial; # double-blind trial; † randomized placebo-controlled trial; IBD: inflammatory bowel disease; CD: Crohn’s disease; UC: ulcerative colitis; CFU: colony forming unit.