Effect of Pretreatment With Lactobacillus Gasseri OLL2716 on First-Line Helicobacter Pylori Eradication Therapy

Ryuzo Deguchi; Hidemasa Nakaminami; Emiko Rimbara; Norihisa Noguchi; Masanori Sasatsu; Takayoshi Suzuki; Masashi Matsushima; Jun Koike; Muneki Igarashi; Hideki Ozawa; Ryuki Fukuda; Atsushi Takagi

Disclosures

J Gastroenterol Hepatol. 2012;27(5):888-892. 

In This Article

Abstract and Introduction

Abstract

Background and Aim: Helicobacter pylori eradication clearly decreases peptic ulcer recurrence rates. H. pylori eradication is achieved in 70–90% of cases, but treatment failures due to poor patient compliance and resistant organisms do occur. Lactobacillus gasseri can suppress both clarithromycin-susceptible and -resistant strains of H. pylori in vitro. The aim of this study was to determine the effect of pretreatment with L. gasseri-containing yogurt on H. pylori eradication. We conducted a randomized, controlled clinical trial in patients with H. pylori infection.
Methods: A total of 229 patients were randomized into either a 1-week triple therapy of rabeprazole (10 mg bid), amoxicillin (750 mg bid), and clarithromycin (200 mg bid) or triple therapy plus L. gasseri-containing yogurt. In the yogurt-plus-triple therapy groups, yogurt containing L. gasseri OLL2716 (112 g) was given twice daily for 4 weeks (3 weeks pretreatment and also 1 week during eradication therapy). Clarithromycin resistance was determined by the detection of a mutation in 23S rRNA using nested polymerase chain reaction and the direct sequencing of DNA from pretreatment feces. H. pylori eradication was diagnosed based on the urea breath test and a stool antigen test after 8 weeks of eradication.
Results: The status of H. pylori susceptibility to clarithromycin was successively determined in 188 out of 229 samples. The rate of infection with clarithromycin-resistant strains of H. pylori was 27.1%. Overall eradication (intention to treat/per protocol) was 69.3/74.5% for the triple-only group, and 82.6/85.6% for the yogurt-plus-triple group (P = 0.018/P = 0.041). Eradication of primary clarithromycin-resistant strains tended to be higher for yogurt-plus-triple therapy than triple-only therapy (38.5 vs 28.0%, respectively, P = 0.458).
Conclusion: This study confirmed that the major cause of treatment failure is resistance to clarithromycin. A 4-week treatment with L. gasseri-containing yogurt improves the efficacy of triple therapy in patients with H. pylori infection.

Introduction

Helicobacter pylori is a Gram-negative bacillus isolated from the gastric mucosa of patients with chronic gastritis.[1] In Japan, approximately 50 million people are estimated to have H. pylori infection, and the infection rate in individuals aged ≥ 50 years is more than 70%.[2]H. pylori is also detected at a high rate in patients with gastric and duodenal ulcers. H. pylori eradication clearly prevents ulcer recurrence, and eradication therapy is now standard in the prevention of peptic ulcer recurrence.[3]H. pylori-positive chronic gastritis is often asymptomatic and has been associated with gastric malignancies, including gastric cancer[4] and mucosa-associated lymphoid tissue (MALT) lymphoma. The annual incidence of gastric cancer in H. pylori-infected patients is about 0.5%, yet adequate treatment of chronic gastritis remains a major problem. First-line treatment for H. pylori eradication typically includes three drugs: a proton pump inhibitor (PPI) and the antibiotics amoxicillin and clarithromycin (CAM). Eradication clearly decreases peptic ulcer recurrence rates.[3] H. pylori eradication is achieved in 70–90% of cases, but treatment failures due to poor patient compliance and resistant organisms do occur. One reason for decreased patient compliance is diarrhea, often associated with antibiotic therapy. In addition, CAM, a first-line drug for community-acquired pneumonia, is widely prescribed for respiratory and oropharyngeal infections, thus increasing drug-resistant organisms. A surveillance study by the Japanese Society for Helicobacter Research reported that approximately 30% of H. pylori infections in Japan are resistant to treatment with CAM.

Probiotics are living microorganisms that improve the intestinal environment and inhibit harmful bacteria. Lactobacilli have been shown to exhibit beneficial effects on the stomach and inhibit H. pylori. H. pylori is able to colonize germ-free mice, but colonization does not occur in specific pathogen free (SPF) mice.[5] In the mouse stomach, Lactobacillus sp. has demonstrated antimicrobial effects against H. pylori in vitro and in mouse models of H. pylori infection.[5,6] We previously reported that yogurt-containing Lactobacillus gasseri (OLL2716) had a suppressive effect on H. pylori infection.[7] The beneficial effects of fermented milk containing Lactobacillus sp. on H. pylori infection have also been reported.[8,9] However, the administration of probiotics alone does not eradicate H. pylori. Recent evidence suggests that supplementation with probiotics could be effective in increasing eradication rates of anti-H. pylori therapy.[10]L. gasseri OLL2716 can suppress both CAM-susceptible and -resistant strains of H. pylori in vitro and in an H. pylori-infected murine model.[11] In order to determine the effect of pretreatment with L. gasseri contained in yogurt on H. pylori eradication, we conducted a randomized, controlled clinical trial in patients with H. pylori infection.

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