ONLINE MANUSCRIPT SUBMISSION
Editorial Board | Instructions for Authors | Main Page | Table of Contents | Archive | Search
The Turkish Journal of Gastroenterology
2010, Volume 21, No 3, Page(s) 212-217
[ Summary ] [ PDF ] [ Similar Articles ] [ Mail to Author ] [ Mail to Editor ]
Efficacy of probiotics in Helicobacter pylori eradication therapy
Bülent YAŞAR1, Evren ABUT2, Hüseyin KAYADİBİ3, Burak TOROS4, Mesut SEZİKLİ1, Züleyha AKKAN1, Özcan KESKİN5, Oya ÖVÜNÇ KURDAŞ1
Department of 1Gastroenterohepatology, Haydarpasa Numune Training and Research Hospital, İstanbul
Department of 2Gastroenterology, Erdem Hospital, Ümraniye, İstanbul
Departments of 3Biochemistry and Clinical Biochemistry, 5İnternal Medicine, Ardahan Military Hospital, Ardahan
Department of 4Gastroenterohepatology, İstanbul Training and Research Hospital, İstanbul
Keywords: Helicobacter pylori, probiotic-containing yogurt, eradication, triple therapy.
Summary
Background/aims: Triple therapy with a proton pump inhibitor, amoxicillin and clarithromycin in Helicobacter pylori eradication is widely accepted, but this combination fails in a considerable number of cases. Our aim was to evaluate whether probiotic-containing yogurt affects the success of eradication. The second aim was to investigate the efficacy of probiotics in the prevention of the side effects related to eradication therapy. Methods: A total of 76 histopathologically proven H. pylori-positive patients enrolled in this study were randomized into two groups. The following regimens were recommended: Group A: pantoprazole (40 mg, b.i.d.), amoxicillin (1000 mg b.i.d.), clarithromycin (500 mg b.i.d.), and 125 ml of probiotic-containing yogurt (Bifidobacterium DN-173 010-1010 cfu/g) before breakfast for 14 days; and Group B: pantoprazole (40 mg, b.i.d.), amoxicillin (1000 mg b.i.d.) and clarithromycin (500 mg b.i.d.) for 14 days. Subjects were asked to report any side effects of therapy during the treatment period. H. pylori status was rechecked four weeks after the completion of the eradication therapy by 13Curea breath test. Results: H. pylori eradication was achieved in 25 of the 38 patients in Group A (66%) and in 20 of the 38 patients (53%) in Group B. Although the success rate was higher in Group A than in Group B, the difference was not significant (p=0.350). The addition of probiotics to the triple therapy significantly lessened the frequency of stomatitis and constipation (p=0.037 and p=0.046, respectively). Conclusions: The addition of probiotic-containing yogurt to the triple therapy did not increase the H. pylori eradication rates for the evaluated dosage and model; however, it decreased the frequency of stomatitis and constipation.
  • Top
  • Summary
  • Introduction
  • Materials And Methods
  • Results
  • Discussion
  • References
  • Introduction
    Helicobacter pylori (H. pylori) infection is a major cause of chronic gastritis and peptic ulcers and is a risk factor for gastric malignancies, adenocarcinoma and mucosa-associated lymphoid tissue lymphoma. It affects nearly 50% of the world’s population (1). H. pylori was classified as a type 1 carcinogen by the World Health Organization in 1994 (2). A remaining question is the high prevalence of H. pylori in developing countries, while its prevalence is decreasing in Western countries (3, 4). Antibiotic resistance due to frequent and uncontrolled use and the high prevalence of antibiotic side effects are the most common causes for treatment failure. To increase the proton pump inhibitor (PPI)-based first-line triple therapy eradication rates, as defined in the Maastricht III Report (5), several clinical trials have been initiated involving extended treatment duration, the use of new antibiotics (quinolone), the use of quadruple therapy as a first option, or the addition of probiotics to triple therapy.

    A probiotic is defined as a living microbial species that, upon administration, may have a positive effect on bowel microecology and improve health conditions (6). Probiotics have several mechanisms by which they can affect H. pylori in vitro (7). The first is that the lactic acid produced by probiotics inhibits H. pylori urease by lowering the gastric pH. The second is that the bacteriocins produced by the lactic acid bacteria kill H. pylori. The third mechanism is the inhibition of the adhesion of H. pylori to gastric epithelial cells. Other mechanisms include the stabilization of the gastric barrier function due to mucin production and an immunologic response (8). In addition, several studies have shown that probiotics can reduce the side effects of antibiotics and improve the treatment tolerability (9, 10).

    In this study, we aimed to determine whether the addition of yogurt containing the probiotic Bifidobacterium DN 173-010 to PPI-based triple therapy affects H. pylori eradication rates and the side effects of antibiotics.
  • Top
  • Summary
  • Introduction
  • Materials And Methods
  • Results
  • Discussion
  • References
  • Materials And Methods
    Patients
    This study was designed as a prospective and randomized trial and included 78 patients who presented to the Haydarpafla Numune Training and Research Hospital Outpatient Clinic with dyspeptic complaints such as heartburn, dyspepsia, nausea, and epigastric pain. Exclusion criteria were: (1) age under 18; (2) previous gastric surgery; (3) allergy to any of the drugs used in the study; (4) receipt of antibiotics, PPIs, H2 receptor blockers, bismuth salts, or probiotics within the previous four weeks; (5) presence of clinically significant conditions such as hepatic, cardiorespiratory, renal, or neoplastic diseases or coagulopathy; and (6) pregnancy or lactation. The protocol was approved by the Ethics Committee of Haydarpafla Numune Training and Research Hospital, and it was concordant with the principles of the Helsinki II Declaration. Informed consent was obtained from all patients.

    Study Method
    All patients found to be eligible for the study underwent esophagogastroduodenoscopy (EGD). The patients who were determined to have esophagitis, gastric or duodenal ulcers, erosion, or tumors were excluded from the study. Two samples were taken from the gastric antrum and corpus for histologic assessment, and the biopsy specimens were fixed in 10% formalin solution. Preparations were stained with hematoxylin-eosin and modified Giemsa stains and were evaluated according to updated Sydney classification.

    H. pylori-positive patients were randomized into two therapy regimens: patients in Group A (n:38) were given pantoprazole (40 mg, b.i.d., before breakfast), amoxicillin (1000 mg b.i.d., after meals), clarithromycin (500 mg b.i.d., after meals), and 125 ml of probiotic-containing yogurt (Bifidobacterium DN-173 010-1010 cfu/g) per day before breakfast for 14 days, whereas patients in Group B (n:38) were given pantoprazole (40 mg, b.i.d., before breakfast), amoxicillin (1000 mg b.i.d., after meals), and clarithromycin (500 mg b.i.d., after meals) for 14 days. Subjects were asked to report any side effects of therapy during the treatment period and were given a possible side effect list, such as epigastric pain, diarrhea, taste disturbance, constipation, and stomatitis. They were also asked to grade each side effect according to severity: mild (effect observed, but could be disregarded), moderate (effect sometimes interfered with daily activities), or severe (effect continuously interfered with daily activities). Patient compliance was evaluated at the end of the treatment by pill count and was considered as completed if >80% of the medication had been taken. Successful eradication was defined as a negative 13C-urea breath test (Helicobacter test INFAI, Bochum, Germany) result four weeks after discontinuation of the therapy.

    Statistical Analysis
    Statistical analyses were performed using the GraphPad Prisma Version 3 packet program. Values were reported as mean ± standard deviation. Non-parametric t-test, chi-square test, and Fisher’s exact test were used to compare two independent groups. All of the reported P-values were twotailed, and those less than 0.05 were considered to be statistically significant.
  • Top
  • Summary
  • Introduction
  • Materials And Methods
  • Results
  • Discussion
  • References
  • Results
    A total of 76 patients (25 males [33%] and 51 females [67%]) were initially included in the study. The patients were randomized into Group A (triple therapy plus probiotic; n:38) and Group B (triple therapy; n:38) for H. pylori eradication. All of the patients in both groups used more than 80% of the therapies, and no patients were lost to followup. There were no statistically significant differences between the two groups regarding age and gender (p=0.586, p=0.625, respectively) (Table 1). H. pylori eradication was achieved in 25 of the 38 (65.8%) patients in Group A and in 20 of the 38 (52.6%) patients in Group B. Although the success rate for H. pylori eradication was higher in Group A than in Group B, the difference was not statistically significant (p=0.350) (Table 2).

    The frequencies of stomatitis (inflammation of the mucosa of the mouth) and constipation, from among the side effects recorded during the therapy period, were significantly lower in Group A than in Group B (p=0.037 and p=0.046, respectively). The differences between the remaining side effects in both groups demonstrated no statistical significance (Table 3).
  • Top
  • Summary
  • Introduction
  • Materials And Methods
  • Results
  • Discussion
  • References
  • Discussion
    The recommended first-line treatment for H. pylori eradication in the published guidelines in Europe and North America is PPI combined with amoxicillin and clarithromycin (5), and this is also the most popular treatment regimen in Turkey. Alarmingly, the rates of eradication with this regimen are falling due to a combination of antibiotic resistance and a poor compliance with therapy, which is primarily due to the side effects of the antibiotics. In a large, randomized, controlled trial performed in Turkey, H. pylori eradication rates achieved with an omeprazole+clarithromycin+amoxicillin regimen for 7 and 14 days were 24% and 43%, respectively (11). A metanalysis by Ayd›n et al. (12) documented that the average H. pylori eradication rate with PPI-based triple regimens was 93.3% in 1996 and decreased to 47.1% in 2004. Decreases in eradication rates may be attributed to antibiotic resistance, especially clarithromycin resistance, which is approximately 28% in Turkey (13). Antibiotic related side effects during anti-H. pylori treatment are common and usually affect the gastrointestinal system. Poor patient compliance due to the side effects and discontinuation of the therapy in the stated time intervals impair the efficiency of the therapy and increase the possibility of resistance development against the antibiotics (14). Additionally, antibiotics can not exhibit their real effects due to insufficient diffusion to the bacteria.

    It has been well documented in studies published since 2000 that some lactobacillus and bifidobacteria species inhibit H. pylori proliferation by means of the secretion of bacteriocin and organic acids (15–18). It has also been established that probiotics interfere with H. pylori adhesion to epithelial cells, increase gastric barrier stabilization and decrease mucosal inflammation. It was reported that the antioxidant and anti-inflammatory effects of probiotics can contribute to gastric mucosa healing (19). Canducci et al. (27) documented that the addition of probiotics to the PPIs and antibiotics increased the eradication rates in 120 H. pylori-positive patients with dyspeptic symptoms, but it did not improve the side effects associated with the therapy. On the other hand, in another study conducted by Armuzzi et al. (21), the addition of probiotics to the first-line therapy did not change the eradication rates, but side effects such as diarrhea, bloating and abnormal taste were lower in the probiotic group than in the control group. The common point in both studies was the use of the lactobacillus species as probiotic. In another study conducted with only clarithromycin by Felley et al. (22), the addition of lactobacillus-containing milk to the clarithromycin decreased the bacterial density and inflammation in the stomach. In studies made only with probiotics, it was shown that probiotics alone could not completely eradicate H. pylori, but they could significantly decrease the bacteria number (16, 17). These findings support the idea that probiotics have inhibitory effects against H. pylori. In light of all these studies, we postulated that the addition of a probiotic-containing yogurt to the H. pylori eradication therapy could increase patient compliance by decreasing the antibiotic-related side effects and could increase the success rates, but there is no absolute consensus on this issue.

    In the present study, the success rate of H. pylori eradication with first-line triple therapy was 53%, and it rose to 66% with the addition of probioticcontaining yogurt. Clearly, the success rate achieved with standard triple therapy is far from the rates that are accepted as ideal. In the studies published in western countries, the success rate of H. pylori eradication therapy was reported as approximately 70%, which is near the ideal values (23). In countries in which frequent and uncontrolled antibiotic utilization is common, as in Turkey, this difference in eradication rates is due to the higher antibiotic resistance.

    One notable point is that most of the studies used the lactobacillus species. In a literature review, we did not find any eradication study using only bifidobacteria, as was used in the present study. The reason for the lactobacillus choice may be their ability to remain 80% alive in the gastric environment for two hours and their stability in acid as compared with other bacteria. In our study, we selected the use of a bifidobacteria-containing product, because bifidobacteria have properties similar to those of lactobacillus and have not yet been used alone in such a study.

    We postulated that giving the probiotic therapy in the morning with the triple therapy might be more useful in keeping the effects of the bacteria at high levels, as the optimum reported pH of the environment should be between 6.5–7.0 for the proliferation of bifidobacteria, and their proliferation is inhibited in a pH below 4.5 (24). For this purpose, the gastric pH would be increased to the desired levels by the PPI, and an optimum environment would be produced for the probiotic proliferation. Therefore, the low eradication rates can be attributed to a low bifidobacteria concentration.

    Another aim in our study was to investigate the efficacy of probiotics for the prevention of the side effects related to the therapy. As mentioned in the Maastricht III Consensus Report, the 14-day treatment is superior to the 7-day treatment. Because of the higher antibiotic resistance rates, developing countries such as Turkey prefer 14-day treatment regimens. This increased duration of therapy carries the burden of increased side effects. It has been shown that the large doses of antibiotics used in the triple therapy change the normal bowel flora. This may account for the adverse events in the gastrointestinal tract (25). It can be speculated that probiotic supplementation may resist this change or diminish the overgrowth of harmful bacteria or yeast induced by the antibiotic treatment. Some previous studies have shown that probiotics have a positive impact on H. pylori eradication therapy-related side effects (26-28). In our study, we did not observe the probiotic therapy to have any effect on the metallic taste, nausea, vomiting, epigastric pain, or diarrhea. However, stomatitis and constipation were significantly lower in the probiotic arm (Group A) than in Group B (p=0.046, p=0.037, retrospectively). This effect is important for those countries in which anti-H. pylori regimens are applied for longer periods (14 days).

    In conclusion, our study suggests that the addition of a probiotic-containing yogurt to triple therapy did not increase the H. pylori eradication rates in the evaluated dosage and model; however, it significantly decreased the frequency of stomatitis and constipation. This suggests a possibility that the addition of probiotic-containing yogurt, commercialized as a kind of food, might be an option for increasing patient compliance, thus encouraging more research in this field.
  • Top
  • Summary
  • Introduction
  • Materials And Methods
  • Results
  • Discussion
  • References
  • References
    1. Go MF, Crowe SE. Virulence and pathogenicity of Helicobacter pylori. Gastroenterol Clin North Am 2000; 29: 64970.

    2. Eslick GD, Lim LL, Byles JE, et al. Association of Helicobacter pylori infection with gastric carcinoma: a metaanalysis. Am J Gastroenterol 1999; 94(9): 2373-9.

    3. Kearney DJ. Retreatment of Helicobacter pylori infection after initial treatment failure. Am J Gastroenterol 2001; 96: 1335–9.

    4. Suerbaum S, Michetti P. Medical progress: Helicobacter pylori infection. N Engl J Med 2002; 347: 1175-86.

    5. Malfertheine P, Megraud F, O’Morain C, et al. Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report. Gut 2007; 56: 772-81.

    6. Lessbros-Pantoflickova D, Corthesy-Theulaz I, Blum AL. Helicobacter pylori and probiotics. J Nutr 2007; 137: 812-8.

    7. Canducci F, Cremonini F, Armuzzi A, et al. Probiotics and Helicobacter pylori eradication. Dig Liver Dis 2002; 34: 81-3.

    8. Kim MN, Kim N, Lee SH, et al. The effects of probiotics on PPI-triple therapy for Helicobacter pylori eradication. Helicobacter 2008; 13: 261-8.

    9. Nista EC, Candelli M, Cremonini F, et al. Bacillus clausii therapy to reduce side-effects of anti-Helicobacter pylori treatment: randomized, double-blind, placebo controlled trial. Aliment Pharmacol Ther 2004; 20: 1181-8.

    10. Cindoruk M, Erkan G, Karakan T, et al. Efficacy and safety of Saccharomyces boulardii in the 14-day triple anti-Helicobacter pylori therapy: a prospective randomized placebocontrolled double-blind study. Helicobacter 2007; 12: 30916.

    11. Gumurdulu Y, Serin E, Ozer B, et al. Low eradication rate of Helicobacter pylori with triple 7-14 days and quadriple therapy in Turkey. World J Gastroenterol 2004; 10: 668-71.

    12. Aydin A, Onder GF, Akarca US, et al. The efficacy of twoweek therapy with ranitidine bismuth citrate, amoxicillin and clarithromycin on Helicobacter pylori eradication in clarithromycin-resistant and -sensitive cases. Turk J Gastroenterol 2005; 16: 203-6.

    13. Baglan PH, Bozdayi G, Ozkan M, et al. Clarithromycin resistance prevalence and Icea gene status in Helicobacter pylori clinical isolates in Turkish patients with duodenal ulcer and functional dyspepsia. J Microbiol 2006; 44: 40916.

    14. Kearney DJ. Retreatment of H. pylori infection after initial treatment failure. Am J Gastroenterol 2001; 96: 1335-9.

    15. Pantoflickova D, Corthesy-Theulaz I, Dorta G, et al. Favourable effect of regular intake of fermented milk containing Lactobacillus johnsonii on Helicobacter pylori associated gastritis. Aliment Pharmacol Ther 2003; 18: 805-13.

    16. Wang KY, Li SN, Liu CS, et al. Effects of ingesting Lactobacillus and Bifidobacterium-containing yogurt in subjects with colonized Helicobacter pylori. Am J Clin Nutr 2004; 80: 737-41.

    17. Gotteland M, Poliak L, Cruchet S, et al. Effect of regular ingestion of Saccharomyces boulardii plus inulin or Lactobacillus acidophilus in children colonised by Helicobacter pylori. Acta Paediatr 2005; 94: 1747-51.

    18. Wendakoon CN, Thomson ABR, Ozimek L. Lack of therapeutic effect of a specially designed yogurt for the eradication of Helicobacter pylori. Digestion 2002; 65: 16-20.

    19. Cats A, Kuipers EJ, Boschaert MA, et al. Effect of frequent consumption of a Lactobacillus casei-containing milk drink in Helicobacter pylori-colonized subjects. Aliment Pharmacol Ther 2003; 17: 429-35.

    20. Sheu BS, Wu JJ, Lo CY, et al. Impact of supplement with Lactobacillusand Bifidobacterium-containing yogurt on triple therapy for Helicobacter pylori eradication. Aliment Pharmacol Ther 2002; 16: 1669-75.

    21. Armuzzi A, Cremonini F, Ojetti V, et al. Effect of Lactobacillus GG supplementation on antibiotic-associated gastrointestinal side-effects during Helicobacter pylori eradication therapy: a pilot study. Digestion 2001; 63: 1-7.

    22. Felley C. Probiotics and Helicobacter pylori. Best Pract Res Clin Gastroenterol 2003; 17: 785-91.

    23. Fontham ETH, Ruiz B, Perez A, et al. Determinants of Helicobacter pylori infection and chronic gastritis. Am J Gastroenterol 1995; 90: 1094-101.

    24. Picard J, Fiaramonti J, Francois A, et al. Review article: Bifidobacteria as probiotic agents-physiological effects and clinical benefits. Aliment Pharmacol Ther 2005; 22: 495512.

    25. Lewis SJ, Freedman AR. Review article: the use of biotherapeutic agents in the prevention and treatment of gastrointestinal disease. Aliment Pharmacol Ther 1998; 12: 80722.

    26. Cremonini F, Di Caro S, Covino M, et al. Effect of different probiotic preparations on anti-Helicobacter pylori therapyrelated side-effects: a parallel group, triple blind, placebocontrolled study. Am J Gastroenterol 2002; 97: 2744-9.

    27. Canducci F, Armuzzi A, Cremonini F, et al. A lyophilized and inactivated culture of Lactobacillus acidophilus increases Helicobacter pylori eradication rates. Aliment Pharmacol Ther 2000; 14: 1625-9.

    28. Huebner ES, Surawicz CM. Probiotics in the prevention and treatment of gastrointestinal infections. Gastroenterol Clin North Am 2006; 35: 355-65.

  • Top
  • Summary
  • Introduction
  • Materials And Methods
  • Results
  • Discussion
  • References
  • [ Summary ] [ PDF ] [ Similar Articles ] [ Mail to Author ] [ Mail to Editor ]
    Editorial Board | Instructions for Authors | Main Page | Table of Contents | Archive | Search