Systematic Review: Are Probiotics Useful in Controlling Gastric Colonization by Helicobacter pylori?

M. Gotteland; O. Brunser; S. Cruchet

Disclosures

Aliment Pharmacol Ther. 2006;23(8):1077-1086. 

In This Article

Clinical Trials With Probiotics In H. Pylori-Colonized Subjects

Clinical trials evaluating the use of different probiotic strains in colonized subjects have been recently reviewed by Hamilton-Miller.[41] In some of these studies, probiotics were used alone while in others they were used as adjunctive agents in the classical treatment of H. pylori infection. The main outcomes of these studies are the rate or the intensity of colonization, changes in the adverse effects associated with antibiotic administration and the intensity of gastric inflammation.

Utilization of Probiotics in Association With Antibiotics in the Treatment of H. Pylori

Of the clinical trials evaluating the association of the classical antibiotic and proton pump inhibitor therapy with probiotics for H. pylori eradication in patients with gastroduodenal pathologies, three were randomized but not placebo controlled ( Table 1 ). This is a critical aspect in the analysis of results because one of the main outcomes evaluated in these studies is the intensity of the adverse effects of the antibiotics and proton pump inhibitors, which has a strong subjective component. Three different probiotics were evaluated in these studies: heat-inactivated L. acidophilus LB,[42]Lactobacillus GG[43] and a yogurt (AB yogurt) containing L. acidophilus La5 and B. lactis Bb12.[44] Results showed that the administration of L. acidophilus LB was associated with a significant increase in the eradication of H. pylori from 72% to 87% (P < 0.02) without decreases in adverse effects. The study using LGG showed a lower incidence of side effects, especially diarrhoea, bloating and taste disturbances without an improved eradication rate. In the trial with the AB yogurt, side effects were less frequent and a higher proportion of patients completed the full week of antibiotic treatment. In the intention-to-treat analysis H. pylori eradication was also higher in the yogurt group (91% vs. 78%, P < 0.05) but this difference disappeared in the per protocol analysis. Fecal bifidobacteria decreased during antibiotic treatment in both groups of patients but in the yogurt group its numbers returned to basal values more rapidly.

Three randomized, double-blind, placebo-controlled studies were carried out with the same objective. Decreases in the side effects of the triple therapy were observed by Cremonini et al.[45] in a study in 85 asymptomatic subjects in whom the effects of a single probiotic (LGG or S. boulardii), or a combination of B. lactis and L. acidophilus administered contemporaneously with the triple therapy for 1 week and continued afterwards for an additional week were tested; similar to previous studies no effect on the clearing of H. pylori was observed. In another study in 53 asymptomatic volunteers, the administration of 180 mL of a L. johnsonii La1-acidified milk (LC-1) twice daily for 3 weeks significantly decreased the density of H. pylori in the gastric mucosa and the intensity and activity of gastric inflammation. Clarithromycin eradicated H. pylori in 26% of the subjects and LC-1 did not improve the effect of the antibiotic.[46] Side effects decreased during supplementation with L. casei DG in the course of quadruple therapy, resulting in a slight improvement of H. pylori eradication.[47]

The results of these studies suggest that probiotic supplementation during anti-H. pylori therapy decreases adverse side effects, resulting in better compliance and, in some cases, improved rates of eradication.

Utilization of Probiotics Alone

Results about the use of probiotics alone in H. pylori-colonized subjects are summarized in Table 2 . The supernatant of a culture of L. johnsonii La1 was tested in double-blind fashion in 20 asymptomatic volunteers who also received omeprazole or a placebo; a decrease in the δ Over the Baseline value (DOB) in the 13C-UBT in comparison with the initial determinations was observed; however, H. pylori was not eradicated from the stomach of the affected individuals.[30]

The effect of L. johnsonii La1 was further explored in asymptomatic infected school children by Cruchet et al. in Chile.[48] In a double blind, randomized, controlled clinical trial, 252 of 326 children (77.3%) 5-16 years of age and H. pylori-positive by 13C-UBT were allocated to one of five groups. Two groups received a product containing live L. johnsonii La1 or L. paracasei ST11 at concentrations >107 CFU/mL every day for 4 weeks; two other groups received the product but with heat-killed La1 or ST11 while the fifth group received the yogurt vehicle as a negative control. A moderate but significant decrease in the results of the 13C-UBT after the treatment compared with basal DOB values was observed in children receiving live La1. The magnitude of the decrease induced by La1 was greater the higher the basal DOB values, suggesting that L. johnsonii La1 exerted a modulating effect on H. pylori colonization by restricting the size of its population in the gastric mucosa. To test whether more frequent intakes exerted a more intense effect, 80 mL of the same commercial preparation was administered to 12 adult asymptomatic volunteers every 2 h for 14 h for 2 weeks.[49] This resulted in higher decreases (40%) in DOB values; as in the previous study, higher initial DOB values correlated with greater decreases in DOB after treatment.

The effect of an La1-acidified milk (LC-1) administration was studied in 50 H. pylori-positive healthy volunteers who did not receive any antibiotic treatment in a randomized, controlled, double-blind study; the histology and H. pylori density from gastric biopsies obtained before and after 3 and 16 weeks of treatment were evaluated.[50] LC1 decreased the severity and activity of the gastritis (P = 0.04) as well as the density of H. pylori colonization. Interestingly, the thickness of the mucus layer increased during LC1 consumption. Altogether, these results suggest that L. johnsonii La1 may reduce the risk of disorders associated with H. pylori and the high risk of gastric inflammation.

Wang et al. observed that of the two probiotic strains present in AB yogurt, Bb12 and La5, only Bb12 exerted an inhibitory effect in vitro against H. pylori.[51] They subsequently administered this yogurt (containing >107 CFU/mL of each strain) to 59 H. pylori-positive individuals twice daily for 6 weeks, while 11 subjects were given a placebo. The authors reported significantly lower DOB values in those receiving the AB yogurt. Moreover, a steeper decrease was observed in those individuals whose initial readings had been the highest, similar to observations by Cruchet et al.[48] and Gotteland and Cruchet[49] with L. johnsonii La1 in asymptomatic volunteers.

Gotteland et al. evaluated with 13C-UBT the effects of S. boulardii plus inulin and of heat-killed L. acidophilus LB in comparison with triple therapy in colonized schoolchildren;[52] the probiotics were administered twice daily for 2 months. Triple therapy eradicated the micro-organism in 66% of the children compared with 12% in those receiving S. boulardii and 6.5% of those receiving L. acidophilus LB. The group receiving S. boulardii also showed a significant decrease in DOB values. To evaluate whether the eradication associated with probiotic intake was a spontaneous process, 81 asymptomatic colonized children were followed with 13C-UBT and without any treatments for 2 months; none of them cleared spontaneously this micro-organism.

Other clinical trials have been carried out with probiotics alone, but with small numbers of subjects and without placebo control. A yogurt containing five strains of lactic acid bacteria with strong in vitro inhibitory activity against H. pylori was investigated by Wendakoon et al.; the intake of 175 mL yogurt thrice daily for 30 days by 27 asymptomatic women resulted in eradication in only one case.[53] Similarly, the administration of a product with L. casei Shirota with anti-H. pylori activity thrice daily for 3 weeks to 14 subjects[54] produced a slight non-significant suppressive effect.

The effect of 90 g of yogurt with L. gasseri OLL2716 (LG21) administered twice daily for 8 weeks in 29 asymptomatic adults was evaluated by means of the 13C-UBT and the pepsinogen I/ II ratio as a marker of gastric inflammation.[55] LG21 decreased significantly DOB values in comparison with baseline measurements and reduced the intensity of gastric inflammation as indicated by the lower pepsinogen I/II ratio. Similar results were obtained with LG21 in children.[56]

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