Probiotics for the Treatment of Helicobacter pylori
Probiotics for the Treatment of Helicobacter pylori
By Jay Udani, MD, and Myles Spar, MD, MPH
Probiotics traditionally are defined as live microorganisms, belonging to the natural gut flora, that have a beneficial effect in the prevention or treatment of specific pathologic conditions when they are ingested. Those used in this manner constitute a small proportion of the more than 500 bacterial species that live symbiotically in the human gut.
Helicobacter pylori is a major etiologic factor in peptic ulcer disease and a risk factor for gastric cancer: The organism causes a six-fold risk of development of this cancer.1 The prevalence of infection in the United States is estimated to be between 45-52%. This gram-negative rod usually begins to colonize the digestive tract during youth, with prevalence increasing throughout life. An estimated 70-80% of elderly adults carry the bacteria.2
Use of probiotics, also called "microbial interference treatment," has been proven effective in the treatment of many gastrointestinal conditions, including infectious diarrhea, inflammatory bowel disease, irritable bowel syndrome, and lactose intolerance.3 This type of therapy was observed by Pasteur and Joubert to be successful as early as 1877, and is now enjoying a resurgence for the treatment of H. Pylori infection, among other conditions.
Conventional Treatment
The National Institutes of Health Consensus Conference in 1994 concluded that all patients with peptic ulcer disease, whether on first presentation, recurrence, or with a history of ulcers, who are H. pylori-positive, should be treated for the infection.4 Treatment with antibiotics requires a 14-day regimen of several medications. The current standard of care involves the use of a proton pump inhibitor with two antibiotics, usually clarithromycin and amoxicillin, with or without bismuth. This protocol achieves more than 90% eradication; however, it requires frequent dosing and is associated with adverse effects. One study demonstrated that 25% of patients treated with standard therapy experience work-limiting side effects, such as rash, photosensitivity, vomiting, neuropathy, and fever.5
Probiotic Identification
The best-studied probiotics are the lactic acid bacteria, Lactobacillus sp., and Bifidobacterium sp. Other organisms used include Escherichia coli, Streptococcus sp., Enterococcus sp., Bacteroides sp., Bacillus sp., Propionibacterium sp., and various fungi (see Table 1, below). Many probiotic preparations contain mixtures of more than one species of bacterium.
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Table 1 |
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Profiles of selected probiotic strains |
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| Strain | Mechanism of Action | Current Uses |
| Lactobacillus acidophilus |
Inhibits attachment; inhibits invasion; competes for nutrients; produces lactic acid and hydrogen peroxide and natural antibiotics |
H. pylori |
| Bifidobacterium bifidum | Inhibits colonization; produces acetic acid; stimulates antibody production; assists in absorption of calcium; helps to rid body of toxins; produces lactic and acetic acid |
Immune system development in formula-fed infants; childhood diarrhea; H. pylori |
| Lactobacillus bulgaricus |
Proteolytic; produces lactic acid; inhibits adhesion; scavenges free radicals; stimulates t-lymphocyte function |
Acid reflux; lactose intolerance |
| Streptococcus thermophilus |
Used to produce yogurt; helps to break down lactose |
Lactose intolerance |
| Lactobacillus ruteri |
Produces lactic acid |
Childhood diarrhea |
| Lactobacillus GG | Produces lactic acid | Irritable bowel syndrome; irritable bowel disease; allergy prevention in newborns; immune system enhancement |
Mechanism of Action
There are many mechanisms by which probiotics assist in antimicrobial action. They include stimulation of immunity, competition for limited nutrients, inhibition of epithelial and mucosal adherence, inhibition of epithelial invasion, and production of antimicrobial substances.6
For the latter several mechanisms, Lactobacillus acidophilus, an anaerobic gram-positive bacterium, has been shown to have an inhibitory effect on the attachment of H. pylori to gastric epithelial cells in vitro.7 L. acidophilus also can produce bacteriocins, which are proteins with antibiotic-like bactericidal properties,8 and lactic acid and hydrogen peroxide, both of which limit the growth of H. pylori.9 In vitro investigation of one type of probiotic, Bacillus subtilis 3, which inhibits H. pylori growth, has shown that this species produces at least two antibiotic substances.10 Some species of lactobacillus can produce nitric oxide and other endotoxins that kill pathologic bacteria.11
In Vitro and Animal Studies
A 1995 study reported inhibition of H. pylori growth by L. acidophilus and Lactobacillus delbrueckii, the latter being a typical milk bacterium found in yogurt cultures.12 Another study examined Clostridium butyricum, a bacterium found among human normal flora, against H. pylori in vitro and in mice. This group showed inhibition of H. pylori adhesion to gastric epithelial cells and cure of H. pylori infection in the mice.7
Clinical Studies
There are several randomized controlled trials (RCTs) and two case series that are especially relevant. Three RCTs and the case series looked at sign and symptom relief and eradication rates, and one trial examined the impact of lactobacillus on side effects from standard triple therapy (see Table 2, below).
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Table 2 |
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Probiotics vs. antibiotics |
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| Parameter | Probiotics | Antibiotic Triple Therapy |
| Tolerance | Excellent | Moderate |
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Safety |
No reported adverse events | Drug interactions, neurotoxicity |
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Side effects |
Minimal |
Nausea, vomiting, rash, photosensitivity, possible neuropathy |
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Cost |
~$35 | ~$95 |
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Efficacy at eradication |
Unproven |
High cure rates in trials (> 90%), lower in clinical practice |
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Antibiotic resistance |
None | Significant |
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Retreatment options |
Ability to advance to use of antibiotics | Repeat same therapy |
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Current role in therapy |
Adjunctive | Primary eradication |
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Quality standard |
Variable | Pharmaceutical |
One RCT enrolled 120 asymptomatic individuals found to be H. pylori-positive during routine screening, who chose to receive eradication therapy.13 They were randomly assigned to one week of treatment with either: 1) rabeprazole (Aciphex, 20 mg twice a day), clarithromycin (250 mg three times a day), and amoxicillin (500 mg three times a day) or 2) the same regimen supplemented with a lyophilized and inactivated culture of L. acidophilus. The dose of lactobacillus was 5 x 109 of inactivated bacterial cells given three times daily for 10 days, including the seven days of the triple therapy plus an additional three days. It was not mentioned whether or not the lactobacillus was given with food or not. Using intent-to-treat analysis with all patients completing therapy, the eradication rate was significantly greater in the group receiving L. acidophilus than in the control group (86.6% vs. 70%; P < 0.05).
In a second RCT, 20 H. pylori-positive subjects were treated with the whey-based L. acidophilus La1 supernatant (50 mL qid) vs. omeprazole (Prilosec, 20 mg qid) plus the La1 for a total of 14 days.14 H. pylori breath tests showed a marked and significant decrease in H. pylori values immediately after treatment in both groups by a similar degree. Unfortunately, there was no placebo control group for the lactobacillus. The study did show a 53-57% decrease in breath test values among all the participants. A prolonged suppression of infection was observed in the group receiving La1 alone vs. the combined therapy group at six weeks after treatment.
The same group looked at using La1-acidified milk (actually, a commercially available yogurt) vs. placebo among 53 volunteers infected with H. pylori.15 The milk/yogurt was given as 180 mL twice a day for three weeks. All the subjects received clarithromycin 500 mg twice daily during the last two weeks of therapy. Esophagogastroduodenoscopy and biopsies were performed at inclusion and repeated 4-8 weeks after the end of treatment. The lactobacillus group had decreased H. pylori densities, antral inflammation, and activity of antral gastritis as compared with placebo (P < 0.05 in each), an effect that persisted for the final follow-up studies. However, the lactobacillus did not improve eradication rates obtained from the antibiotic.
In 2001, Sakamoto et al examined the use of Lactobacillus gasseri (LG21) in a case series of 31 subjects who were H. pylori-positive by urea breath test and serology.16 In the first part, 90 g of yogurt containing 1-1.4 x 107 colony forming units/g of LG21 was consumed twice daily for eight weeks following eight weeks of yogurt without the bacteria. Serial urea breath tests showed significantly lower values after the LG21 yogurt, but these levels rose again three months later in three of the subjects. Measures of gastric mucosal inflammation were significantly lower after the eight weeks of LG21 yogurt as compared to the period after the plain yogurt. Examination of antral biopsies showed two- to 100-fold decreases in numbers of H. pylori, but in no case were bacteria eradicated completely.
Finally, Armuzzi et al used a strain of Lactobacillus GG in a study of 120 patients to compare side effects from triple therapy alone (one week of pantoprazole [Protonix] 40 mg twice daily, clarithromycin 500 mg twice daily, and tindazole 500 mg twice daily) or to the same regimen supplemented with Lactobacillus GG for 14 days.17 The dose of lactobacillus was 6 x 109 of viable bacteria, given twice daily, two hours after breakfast or dinner during the week of eradication therapy and the following week. Patients completed validated questionnaires during follow-up to determine the type and severity of side effects. The lactobacillus group was found to have significantly less diarrhea (6.6% vs. 23.3%), bloating (16.6% vs. 40%), and taste disturbances (6.6% vs. 26.6%), all with P values < 0.05.
Toxicity/Safety (Adverse Effects)
Probiotics are well tolerated. Trials of more than 2,000 healthy normal adult volunteers have shown no harmful effects.18 A 1996 study in which lactobacilli were found to aggregate platelets has been disproved.19
Still, some reports have isolated bacteria used in probiotics from human infections, though it is felt that these represented opportunistic infections.20 Lactobacillus GG, specifically, has no invasive properties. Although no reports of allergic reaction to probiotics were found in the literature reviewed, many of these species are delivered in a preparation containing lactose and milk proteins, which have allergic potential.
There are few known drug interactions from the use of probiotics. However, L. acidophilus has been shown to interfere with the metabolism of sulfasalazine and chloramphenicol by degrading these drugs in the stomach if taken concurrently.20
Preparation
Aside from freeze-dried powder, there are many sources of probiotics, including fermented milk products such as yogurt, kefir and cheese, as well as miso and tempeh.21 Because the pasteurization process kills these organisms, they must be introduced after pasteurization.
Formulation and Dosage
DNA studies have revealed great genetic variability within strains of L. acidophilus and other probiotic species. The use of specific strains corresponding with those used in research studies is recommended. In addition, the method of packaging and storing the product is important, as temperature, moisture, light, and air can adversely affect viability. Refrigeration of the product from the time of manufacture through delivery and storage is critical to ensure the potency of the strains, as temperatures above 60° F (15° C) will kill many of the bacteria.22 The products should be kept in amber-colored glass bottles to avoid light damage unless specifically designed by the manufacturer to be stable on the shelf in some other packaging.
Quality, however, is a problem. One study reported recently that of 30 dried probiotic supplements tested, 11 contained no viable bacteria, seven contained all claimed species, and 18 had species other than those on the label. Another group found that 63% of products tested in the United Kingdom were below standard.23
In general, probiotics should be taken alone, on an empty stomach, two to three hours after an antibiotic dose to avoid killing the probiotic bacteria. It is suggested to limit the dosage to fewer than 10 billion viable L. acidophilus daily to decrease any risk of possible mild gastrointestinal disturbance.8
Patients should be encouraged to use those probiotics that have been studied in clinical trials. The products should be formulated by respected manufacturers that subject their products to independent quality control and guarantee potency, purity, and correct labeling. Probiotics in the form of encapsulated supplements should relate closely to the individual forms studied in clinical trials.
Conclusion
H. pylori is one of the world’s most common pathogens. Probiotics, supplements, or foods containing indigenous flora and used for treatment or prevention of disease, have been shown in in vitro and animal studies to inhibit H. pylori growth and even to eradicate the organism. Human studies have begun to confirm these findings, but there still is limited evidence from controlled clinical trials and there are no firm data suggesting that probiotic therapy by itself would be as effective as standard therapy for eradication of H. pylori infection. These studies do indicate that probiotics, especially lactobacilli, may decrease side effects and enhance efficacy of conventional eradication therapy.
Recommendation
The use of probiotics is recommended as an adjunct to currently proven standard care for H. pylori infection. Except for risk of allergic reaction, these products have minimal adverse effects, and are able to counteract some of the side effects from triple therapy. Studies to determine the efficacy of probiotics in eradicating H. pylori infection are under way.
Dr. Udani and Dr. Spar are Clinical Instructors, University of California Los Angeles School of Medicine; Dr. Udani also is Medical Director, Northridge Hospital Integrative Medicine Program, Northridge, CA.
References
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19. Moilanen E, et al. Effect of Lactobacillus GG on platelet aggregation. Nutr Today 1996;31:43S-44S.
20. Ishibashi N, Yamazaki S. Probiotics and safety. Am J Clin Nutr 2001;73:465S-470S.
21. Murray M. Probiotics: Acidophilus, bifidobacter, and FOS. Am J Nat Med 1996;3:14-19.
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Udani J, Spar M. Probiotics for the treatment of Helicobacter pylori. Altern Med Alert 2002;5:57-61.Subscribe Now for Access
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