Table 1.
Clinical trials in children using probiotics as a complement during Helicobacter pylori eradication treatment
| Ref. | Study design | Therapy | Probiotic strain (product; dose; time) | Patients | Diagnosis | No. of treated patients | Eradication n (%); P value | Side effects n (%); P value | Test for confirming eradication (time after completion of therapy) |
| Sýkora et al[56] | P, R, DB, PC | A (25 mg/kg twice daily), C (7.5 mg/ kg twice daily), and O (10 or 20 mg twice daily) 1 wk + probiotic vs same eradication therapy + placebo | L. casei DN-114 001 1010 CFU in 100 mL of fermented milk (actimel, Danone); 2 wk | 86 (aged 9-15 yr) symptomatic children and adolescents | EGDS (histopathology, culture, and RUT) and HpSA | 391 362 vs 471 442 | 33 (84.6)1 33 (91.6)2 vs 27 (57.5)1; 0.0045 27 (61.3)2; 0.0019 | 9 (23.1) vs 10 (21.2); NS (nausea, headache, abdominal pain, recurrent vomiting, diarrhoea) | HpSA and 13C-UBT (4 wk) |
| Gotteland et al[64] | O, R | A (50 mg/kg tid), C (15 mg/kg bid), and L (1 mg/kg bid) 8 d vs Probiotic vs Symbiotic | Lactobacillus acidophilus LB (LB); capsule containing 109 heat-killed and lyophilized LB (Lacteol Forte, Laboratoire du Dr. Boucard, Paris, France); b.i.d. for 8 wk, and Saccharomyces boulardii plus inulin (SbI); sachet containing 250 mg of lyophilized Sb (Perenteryl, Merck Quìmica Chilena, Santiago, Chile); bid for 8 wk | 141 (aged 5-12 yr) asymptomatic children. 81 children were observed without any treatment | 13C-UBT | 452 vs 462 vs 502 | 30 (66)2 vs 3 (6.5)2 vs 6 (12)2; < 0.001 No spontaneous clearance was observed in children without treatment | NA | 13C-UBT (1 d) |
| Goldman et al[58] | R, DB, PC | A (50 mg/kg per day), C (20 mg/kg per day bid), and O (1 mg/kg per day) 1-wk + probiotic vs same eradication therapy + placebo | Bifidobacterium animalis and Lactobacillus casei (107 CFU/mL) in 250 mL of a commercial yogurt; once daily for 3 mo | 65 (aged 5-15 yr) symptomatic children and adolescents | EGDS and 13C-UBT (histological data NA) | 3312 vs 3212 | 15 (45.5)12 vs 12 (37.5)12; 0.345 at 1 mo 14 (42.4)12 vs 13 (40.6)1,2; 0.542 at 3 mo | NA | 13C-UBT ( 1 and 3 mo) |
| Lionetti et al[57] | R, DB, PC | O (1 mg/kg/die) plus A (50 mg/kg/die) for 5 d followed by O (1 mg/kg/die) plus C (15 mg/kg/die)and T (20 mg/kg/die) for the next 5 d + probiotic vs same eradication therapy + placebo | L. reuteri [pill containing 108 CFU of L. reuteri ATCC 55730 (SD2112), Reuterin, Nòos]; one pill once daily for a period of 20 d | 40 (aged 3.3-18 yr) symptomatic children and adolescents | EGDS (histopathology and RUT) [pangastritis (27); antral gastritis, mild (20); antral gastritis, moderate (14); antral gastritis, severe (10)] | 2012 vs 2012 | 17 (85)12 vs 16 (80)12; NS | Reduction of GSRS score during eradication therapy [4.1 ± 2 (95%CI: 2.9-5.9) vs 6.2 ± 3 (95%CI: 5.2-8.3); P < 0.01] and at the end of follow-up [3.2 ± 2 (95%CI: 2.4-4) vs 5.8 ± 3.4 (95%CI: 4.8-6.9); P < 0.009]; Epigastric pain (15% vs 45%; P < 0.04); Abdominal distension (0% vs 25%; P < 0.02); Eructation (5% vs 35%; P < 0.04); Disorders of defecation (15% vs 45%; P < 0.04); Halitosis (5% vs 35%; P < 0.04) | 13C-UBT (8 wk) |
| Hurduc et al[60] | O, R | A (50 mg/kg per day, bid) and C (15 mg/kg per day, bid) 7-10 d; O or E (1 mg/kg per day, bid) 3-wk + probiotic vs same eradication therapy + placebo | Saccharomyces boulardii, Enterol, Biocodex, Gentilly Cedex; 250 mg bid; 4-wk | 90 (aged 3-18 yr) children and adolescents with dyspepsia | EGDS (histopathology and RUT) [chronic gastritis: mild (8); moderate-to-severe (82); active (32); inactive (58)] | 4812 vs 4212 | 45 (93.3)12 vs 34 (80.9)12; NS | 4 (8.3) vs 13 (30.9); P = 0.047 (bloating, taste disturbance, nausea, abdominal pain, diarrhoea, constipation, loss of appetite, fatigue) | EGDS (4-6 wk) (histopathology and RUT) |
| Szajewska et al[59] | R, DB, PC | A (50 mg/kg per day bid), C (20 mg/kg per day bid), and O (1 mg/kg per day) 1-wk + probiotic vs same eradication therapy + placebo | Lactobacillus GG 1 × 109 CFU; 7 d | 83 (aged 5-17 yr) symptomatic children and adolescents. Excluded from the analysis were 17 children for lack of diary and/or 13C-UBT | EGDS (2 of 3 tests - 13C-UBT, histopathology or RUT) [histological data NA] | 342 vs 322 | 23 (69)2 vs 22 (68); RR = 0.98 (95%CI: 0.7-1.4)2 | Therapy-related diarrhea: 2 (6) vs 6 (20); P = NS Total side effects: 18 (51.4) vs 13 (40.6); P = NS Abdominal pain: 0 vs 0 Nausea: 4 (11.4) vs 3 (9.4); P = NS Vomiting: 2 (5.7) vs 1 (3.1); P = NS Constipation: 2 (5.7) vs 2 (6.2); P = NS Flatulence: 3 (8.6) vs 1 (3.1); P = NS Taste disturbance: 4 (11.4) vs 5 (15.6); P = NS Loss of appetite: 3 (8.6) vs (3.1); P = NS Need for discontinuation of therapy: 0 vs 0 | 13C-UBT (4 wk) |
| Tolone et al[61] | R | A (50 mg/kg per day bid), C (15 mg/kg per day bid), and O (1mg/kg per day) 1-wk + probiotic vs same eradication therapy + placebo | Lactobacillus Plantarum 5 × 109, L. reuterii 2 × 109, L. casei subsp. Rhamnosus 2 × 109, Bifidobacterium infantis and B. longum 2 × 109, L. salivarius 1 × 109, L. acidoPhilus 1 × 109, Streptococcus termophilus 5 × 109, and L. sporogenes 1 × 109 + inuline as a prebiotic (5 g/dayose q.d., Probinul , Cadigroup); 7 d | 68 (mean age, 8.3 yr) children with heartburn, dyspepsia, nausea and epigastric pain | EGDS (histopathology) [histological data: NA] | 3412 vs 3412 | 30 (88.2)12 vs 26 (76.4)12; 0.1 | Epigastric pain: 2 (5.8) vs 6 (17.6); P < 0.05 Nausea: 1 (2.9) vs 3 (8.8); P < 0.05 Vomiting : 0 vs 2 (5.8); P < 0.05 Diarrhea: 0 vs 8 (23.5); P < 0.05 | 13C-UBT (4 wk) |
| Ahmad et al[62] | R, DB, PC | A (50 mg/kg per day bid) and F (6 mg/kg per day bid) 1-wk; O (1 mg/kg per day) 4-wk + probiotic vs same eradication therapy + placebo | Lactobacillus acidophilus, L. rhamnosus, L. bulgaricus, L. casei, Streptococcus thermophilus, Bifidobacterium infantis, B. breve; 1 × 109 CFU/1 sachet, Protexin Co; 4 wk | 66 (aged 3-14 yr) children with chronic abdominal pain, gastrointestinal bleeding, unexplained frequent vomiting and unexplained iron deficiency anemia | EGDS (positive RUT or histopathology) [Antral nodularity (57); Gastric erythema (16); Duodenal ulcer (14); Gastric ulcer (1)] | 3312 vs 3312 | 30 (90.1)12 vs 23 (69.7)12; 0.04 | ConstiPation: 2 (5.8) vs 2 (5.8); P = NS Nausea/vomiting: 2 (6.1) vs 9 (27.3); P = 0.02 Diarrea: 2 (6.1) vs 8 (24.2); P = 0.04 Abdominal bloating: 3 (9.1) vs 4 (12.1); P = 1 | HpSA (4-8 wk) |
1
Intention-to-treat analysis;
2
Per-protocol analysis. O: Open; R: Randomized; DB: Double-blind; SB: Single blind; PC: Placebo controlled; P: Prospective; A: Amoxicillin; C: Clarithromycin; F: Furazolidone ; M: Metronidazole; T: Tinidazole; O: Omeprazole; E: Esomeprazole; L: Lansoprazole; CFU: Colony forming units; RUT: Rapid urease test; UBT: Urea breath test; H. Pylori: Helicobacter pylori; HpSA: H. Pylori stool antigens; GSRS: Gastrointestinal symptom rating scale; NA: Not available; L. johnsonii: Lactobacilli johnsonii; L. paracasei: Lactobacilli paracasei.