Homan and Orel Journal Review
Reviewed by Ronald Sherman, M.D.
Matjaž Homan, Rok Orel. Are probiotics useful in Helicobacter pylori eradication? World J Gastroenterol. 2015; 21(37): 10644-10653.
Helicobacter pylori (H. pylori) is considered an etiologic factor for the development of peptic ulcer disease, gastric adenocarcinoma, and MALT lymphoma. Therapeutic schemes to eradicate the bacteria are based on double antibiotic therapy and proton pump inhibitor. Despite many therapeutic improvements in H. pylori eradication treatment, it is still associated with high infection rate also in developed countries. Bacterial resistance and adverse events occurrence are among most frequent causes for anti- H. pylori treatment failure. Several studies have reported that certain probiotic strains can exhibit inhibitory activity against H. pylori bacteria. In addition, some probiotic strains can reduce the occurrence of side effects due to antibiotic therapy and consequently increase the H. pylori eradication rate. The results of the prospective double-blind placebo-controlled studies suggest that specific probiotics, such as S. boulardii and L. johnsonni La1 probably can diminish the bacterial load, but not completely eradicate the H. pylori bacteria. Furthermore, it seems that supplementation with S. boulardii is a useful concomitant therapy in the standard H. pylori eradication treatment protocol and most probably increases eradication rate. L. reuteri is equally effective, but more positive studies are needed. Finally, probiotic strains, such as S. boulardii, L. reuteri and L. GG, decrease gastrointestinal antibiotic associated adverse effects.
Helicobacter pylori (H. pylori) is a Gram-negative bacterium associated with gastric (stomach) colonization and infection. It is common world-wide, especially in Asia, Africa and Eastern Europe, though its prevalence in North American and Western European adults is only about 30%. Its medical significance comes from the fact that in about 20% of cases it causes symptomatic gastritis, ulcers, stomach cancer (adenocarcinoma and non-Hodgkin’s gastric Lymphoma). H. pylori is also associated with iron deficiency anemia, idiopathic thrombocytopenic purpura, and vitamin B12 deficiency.
Eradication of H. pylori is associated with reductions of symptomatic disease and cancer. Therapy generally consists of taking two or more antibiotics plus a proton pump inhibitor (to reduce stomach acid production) for one to three weeks. Unfortunately, the frequency of treatment failures is rising, due primarily to two factors: 1) increasing antimicrobial resistance, and 2) difficulty tolerating the treatment, which leads to premature termination or non-compliance with the regimen. In addition, even successful eradication is often followed by reinfection, since H. pylori is often acquired from the environment, and the environment does not change with treatment of the infected individual. Therefore, there is a need for alternative methods of H. pylori prevention and eradication.
Recent studies suggest a possible role for probiotics in the eradication of H pylori. A review of such studies was the goal of the authors of this paper. This was not a systematic review, and no description was provided to describe their methods of literature search or analysis.
The authors described the presence of Lactobacillus species in the normal gastric biome, and suggested that they probably help to maintain gastric health. The authors then reviewed a variety of mechanisms by which Lactobacillus and other probiotics might help in H. pylori suppression or eradication: 1) decreasing the gastric inflammatory response to H. pylori, by reducing inflammatory cytokine secretion and reducing immunoglobulin (antibody) production; 2) secreting antibacterial substances such as lactic acid, short chain fatty acids, hydrogen peroxide and bactericins; 3) inhibiting H. pylori urease production and activity, due to the pH lowering effect of lactic acid; 4) increasing mucin production, which counteracts the mucous-dissolving activity of H. pylori; 5) competing with H. pylori strains for gastric binding sites; or 6) removing (cleaving) those binding sites altogether.
Finally, the authors reviewed the possible roles of probiotics in H. pylori treatment by reviewing clinical studies of probiotics used alone as H. pylori treatment, and studies using probiotics in combination with conventional antibiotic / proton pump inhibitor therapy. Some probiotics (especially Saccharomyces boulardii and L. johnsonni La1) were associated with significant reductions in H. pylori colonization, though usually did not completely eradicate the infection.
When used as adjuvants (that is, in combination) with conventional pharmacotherapy, multiple clinical trials and meta-analyses demonstrate a small but significant improvement in cure rates, compared to conventional antibiotic therapy alone. In most of these studies, it was presumed that the major mechanism for this benefit was that the probiotics were reducing gastrointestinal side effects of the antibiotic treatment (the probiotics being associated with reduced diarrhea, bloating, etc.), and thereby improved compliance with the difficult treatment regimen. The authors also reviewed multiple studies demonstrating no added benefit from probiotics.
The authors are to be commended for their detailed review of current literature regarding probiotic use in H pylori therapy. The review appears unbiased (based on the presentation of conflicting data and opinions, where they exist. However, the absence of an objective protocol by which the review was conducted (or at least the absence of a description of that protocol) makes it impossible to know for sure what or where any possible biases may exist.
The authors write that:
“The eradication rates achieved by classic triple therapy consisted from proton pump inhibitor and double antibiotic therapy are quite low and range from 60% to 80% . . . . Antibiotic-associated gastrointestinal adverse events are the major cause for lower compliance . . . . So far, mostly different types of Lactobacillus and Saccharomyces boulardii were tested. [These] probiotics most probably decrease the bacterial load but don’t eradicate H. pylori completely in the gastric mucosa, if they are used as monotherapy. On the contrary, some probiotics when added to classical triple therapy may increase eradication rates. A reasonable amount of evidence exists that supplementation with S. boulardii is a useful concomitant therapy in the standard H. pylori eradication treatment protocol and most probably increases the eradication rate. L. reuteri is also a good candidate for adjunctive therapy, but more positive studies are needed. The effect of other probiotics strains is less well described. Side effects, caused by double antibiotic therapy, can be lowered with probiotics. Probiotic strains, such as Saccharomyces boulardii, Lactobacillus reuteri and L. GG, decrease gastrointestinal antibiotic associated adverse effects, especially diarrhoea. [Some studies and opinion leaders suggest] that . . . probiotics and prebiotics show promising results as an adjuvant treatment [by reducing] side effects.”
This appears to be a very reasonable, yet conservative interpretation. Used as an adjuvant, these probiotics have improved the success rate of H. pylori eradication by as much as 10% (i.e., 80% vs 70% in some comparative trials). Even adjuvant yogurt has resulted in improved efficacy rates (though, as the authors point out, other studies with co-administered yogurt have shown no benefit).
What the authors do not discuss is the potential role of probiotics in the recurrence of H. pylori infection. Recurrence is common because H. pylori is acquired through ingestion of the bacteria from the environment (i.e., with food), and most people return to the same environment and food habits following their treatment of infection. Though more difficult to perform (due to the need for larger populations and longer follow-up), I would like to see more studies of probiotic use as a preventive or prophylactic intervention for re-acquisition of H. pylori, and a review of such studies to date. Since patients already treated for H. pylori have demonstrated themselves to be symptomatic (easily identifiable) and at risk (presumably with a higher rate of future infection than would be seen in the general population), re-acquisition studies would at least be easier and less expensive to conduct than prevention studies that focus on the general population.
To view other articles reviewed in this and other issues of the Biotherapy Journal Review, visit http://www.bterfoundation.org/jforum.