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


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

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In the present study, 4-week pretreatment with yogurt containing L. gasseri before triple therapy improved the eradication rates. The use of probiotics for H. pylori infection was first adopted following a series of research studies in germ-free mice. The studies reported that H. pylori colonizes germ-free but not SPF mice, and that Lactobacillus in the stomach of SPF mice inhibits colonization by H. pylori.[5,6] In a subsequent study involving human volunteers, L. gasseri (OLL2716) decreased the H. pylori density and improved gastritis.[7] Several studies also reported that the ingestion of fermented milk containing Lactobacillus improved H. pylori-infected gastritis, but eradication was not successful, and, after stopping ingestion, this effect on H. pylori suppression was lost. Recent evidence revealed that supplementation with probiotics could be effective in increasing eradication rates due to anti-H. pylori therapy. Tong et al.[10] conducted a meta-analysis of supplemental probiotics in eradication therapy. Among 14 randomized trials, the eradication rates for eradication therapy alone and eradication therapy with probiotics were 74.8 and 83.6%, respectively. With combined treatment, the eradication rate increased, and adverse effects, such as diarrhea, decreased. However, the eradication rate varies by protocol. Typically, probiotics were given during the eradication therapy or following 3–4 weeks.[16–18] In contrast, Sheu et al.[19] reported that pretreatment with Lactobacillius and Bifidobacterium-containing yogurt improved the efficacy of quadruple therapy after failed triple therapy. They also demonstrated a decreased bacterial load after pretreatment with yogurt. Therefore, we chose a protocol involving pretreatment with L. gasseri-containing yogurt. Based on ITT analysis, eradication rates in the yogurt-plus-triple and triple-therapy-only groups were 82.6% and 69.3%, respectively (P = 0.018) ( Table 3 ). PP analysis also showed that H. pylori eradication rates in the yogurt-plus-triple group (85.6%) were significantly higher than those in the triple-therapy-only group (74.5%) (P = 0.046).

The mechanism by which probiotics reduce H. pylori-related gastric mucosal injury has not been elucidated. Gastric mucosal inflammation due to H. pylori infection is primarily mediated by cytokines. Cytokines involved in the clinical manifestations of H. pylori infection of the gastric epithelium include interleukin (IL)-1, IL-8, and tumor necrosis factor.[20,21] In H. pylori infection, neutrophil infiltration is a characteristic histologic finding. IL-8 is a neutrophil chemotactic factor produced by H. pylori-infected gastric epithelium. Previously, we reported IL-8 concentrations in the gastric mucosa measured before and after L. gasseri-containing yogurt consumption. L. gasseri consumption significantly decreased IL-8, whereas with a placebo, there was no decrease in IL-8.[22] In that 8-week study, although eradication was not observed, some volunteers showed histologic improvement of gastritis.

The major cause of eradication failure was CAM-resistance due to mutation of the 23S rRNA gene. Eradication rates of CAM-susceptible H. pylori were high in both groups ( Table 4 ). Eradication rates of primary CAM-resistant strains tended to be higher in the yogurt-plus-triple group than that in triple-only group (38.5 vs 28.0%, respectively, P = 0.428). The detection of CAM-resistance based on analyzing feces is a non-invasive method. Furthermore, mixed infections with both CAM-susceptible and -resistant H. pylori were detected in 13 patients.

In mixed infections with both CAM-susceptible and -resistant H. pylori, the eradication rate in the yogurt-plus-triple group was 50% (3/6), however, that in the triple-therapy-only group was 0% (0/4).

In conclusion, our data suggested that supplementation with yogurt containing L. gasseri is effective for first-line eradication therapy. A further large-scale study is required to clarify the effectiveness of L. gasseri against CAM-resistant H. pylori infection.


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