Probiotics for the treatment of Helicobacter pylori infection in children

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 362vs 471 442	33 (84.6)1 33 (91.6)2vs 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	452vs 462vs 502	30 (66)2vs 3 (6.5)2vs 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)	3312vs 3212	15 (45.5)12vs 12 (37.5)12; 0.345 at 1 mo 14 (42.4)12vs 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)]	2012vs 2012	17 (85)12vs 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)]	4812vs 4212	45 (93.3)12vs 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]	342vs 322	23 (69)2vs 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]	3412vs 3412	30 (88.2)12vs 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)]	3312vs 3312	30 (90.1)12vs 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)

¹Intention-to-treat analysis;

²Per-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.