H. pylori treatment reduces the prevalence of precancerous gastric lesions and may reduce gastric cancer incidence, but further data are needed to prove the latter point. Long-term vitamin or garlic supplementation had no beneficial effects on the prevalence of precancerous gastric lesions or on gastric cancer incidence.

ObjectiveGastrointestinal microbiota may be involved in Helicobacter pylori-associated gastric cancer development. The aim of this study was to explore the possible microbial mechanisms in gastric carcinogenesis and potential dysbiosis arising from H. pylori infection.DesignDeep sequencing of the microbial 16S ribosomal RNA gene was used to investigate alterations in paired gastric biopsies and stool samples in 58 subjects with successful and 57 subjects with failed anti-H. pylori treatment, relative to 49 H.pylori negative subjects.ResultsIn H. pylori positive subjects, richness and Shannon indexes increased significantly (both p<0.001) after successful eradication and showed no difference to those of negative subjects (p=0.493 for richness and p=0.420 for Shannon index). Differential taxa analysis identified 18 significantly altered gastric genera after eradication. The combination of these genera into a Microbial Dysbiosis Index revealed that the dysbiotic microbiota in H. pylori positive mucosa was associated with advanced gastric lesions (chronic atrophic gastritis and intestinal metaplasia/dysplasia) and could be reversed by eradication. Strong coexcluding interactions between Helicobacter and Fusobacterium, Neisseria, Prevotella, Veillonella, Rothia were found only in advanced gastric lesion patients, and were absent in normal/superficial gastritis group. Changes in faecal microbiota included increased Bifidobacterium after successful H. pylori eradication and more upregulated drug-resistant functional orthologs after failed treatment.ConclusionH. pylori infection contributes significantly to gastric microbial dysbiosis that may be involved in carcinogenesis. Successful H. pylori eradication potentially restores gastric microbiota to a similar status as found in uninfected individuals, and shows beneficial effects on gut microbiota.

Objective To assess the effects of Helicobacter pylori treatment, vitamin supplementation, and garlic supplementation in the prevention of gastric cancer. Design Blinded randomized placebo controlled trial. Setting Linqu County, Shandong province, China. Participants 3365 residents of a high risk region for gastric cancer. 2258 participants seropositive for antibodies to H pylori were randomly assigned to H pylori treatment, vitamin supplementation, garlic supplementation, or their placebos in a 2×2×2 factorial design, and 1107 H pylori seronegative participants were randomly assigned to vitamin supplementation, garlic supplementation, or their placebos in a 2×2 factorial design. Interventions H pylori treatment with amoxicillin and omeprazole for two weeks; vitamin (C, E, and selenium) and garlic (extract and oil) supplementation for 7.3 years (1995-2003). Main outcome measures Primary outcomes were cumulative incidence of gastric cancer identified through scheduled gastroscopies and active clinical follow-up through 2017, and deaths due to gastric cancer ascertained from death certificates and hospital records. Secondary outcomes were associations with other cause specific deaths, including cancers or cardiovascular disease. Results 151 incident cases of gastric cancer and 94 deaths from gastric cancer were identified during 1995-2017. A protective effect of H pylori treatment on gastric cancer incidence persisted 22 years post-intervention (odds ratio 0.48, 95% confidence interval 0.32 to 0.71). Incidence decreased significantly with vitamin supplementation but not with garlic supplementation (0.64, 0.46 to 0.91 and 0.81, 0.57 to 1.13, respectively). All three interventions showed significant reductions in gastric cancer mortality: fully adjusted hazard ratio for H pylori treatment was 0.62 (95% confidence interval 0.39 to 0.99), for vitamin supplementation was 0.48 (0.31 to 0.75), and for garlic supplementation was 0.66 (0.43 to 1.00). Effects of H pylori treatment on both gastric cancer incidence and mortality and of vitamin supplementation on gastric cancer mortality appeared early, but the effects of vitamin supplementation on gastric cancer incidence and of garlic supplementation only appeared later. No statistically significant associations were found between interventions and other cancers or cardiovascular disease. Conclusions H pylori treatment for two weeks and vitamin or garlic supplementation for seven years were associated with a statistically significant reduced risk of death due to gastric cancer for more than 22 years. H pylori treatment and vitamin supplementation were also associated with a statistically significantly reduced incidence of gastric cancer. Trial registration ClinicalTrials.gov NCT00339768 .

Helicobacter pylori infection and the cytokine-mediated inflammatory responses play important roles in gastric cancer pathogenesis. This case control study was conducted to assess the association between genetic polymorphisms in interleukin (IL)-1B, IL-1RN, IL-8, IL-10 and tumor necrosis factor alpha (TNFalpha), which are involved in H.pylori infection, and risk of gastric cancer. Genotypes were determined by PCR-based denaturing high-performance liquid chromatography analysis and direct DNA sequencing in 250 incident cases with gastric cancer and 300 controls recruited in Northern China. Serum levels of anti-H.pylori IgG and IgA were measured by enzyme-linked immunosorbent assay to indicate H.pylori infection. We found that the risk of gastric cancer was significantly elevated in subjects with the IL-8-251 AA [adjusted odds ratio (OR) 2.02; 95% confidence interval (CI) 1.27-3.21] or IL-10-1082 G (OR 2.02; 95% CI 1.24-3.29) or TNFalpha-308 AG (OR 1.81; 95% CI 1.04-3.14) genotype. An elevated risk of gastric cancer was observed in subjects with H.pylori infection and the IL-8-251 AA genotype (OR 2.54; 95% CI 1.38-4.72) or IL-10-1082 G carriers (OR 2.62; 95% CI 1.42-4.93). An increased OR was also suggested for IL-1B-31 and TNFalpha-238, but confidence intervals included the null value. There was no evidence of increased risk for any of the other polymorphisms evaluated. These findings suggest that genetic polymorphisms in IL-8, IL-10 and TNFalpha may play important roles in developing gastric cancer in the Chinese population.

Objective To clarify the full range of benefits and adverse consequences of Helicobacter pylori eradication as a strategy for gastric cancer prevention, the community-based intervention trial was launched in Linqu County, China. Design A total of 184 786 residents aged 25-54 years were enrolled in this trial and received 13 C-urea breath test. H. pylori positive participants were assigned into two groups, either receiving a 10-day quadruple anti-H. pylori treatment or lookalike placebos together with a single dosage of omeprazole and bismuth. Results The prevalence of H. pylori in trial participants was 57.6%. A total of 94 101 subjects completed the treatment. The overall H. pylori eradication rate was 72.9% in the active group. Gender, body mass index, history of stomach disease, baseline delta over baselinevalue of 13 C-urea breath test, missed medication doses, smoking and drinking were independent predictors of eradication failure. The missed doses and high baseline delta over baseline-value were important contributors in men and women (all P trend <0.001). However, a doseresponse relationship between failure rate and smoking or drinking index was found in men (all P trend <0.001), while high body mass index (P trend <0.001) and history of stomach disease were significant predictors in women. The treatment failure rate increased up to 48.8% (OR 2.87, 95% CI 2.24 to 3.68) in men and 39.4% (OR 2.67, 95% CI 1.61 to 4.42) in women with multiple factors combined. Conclusions This large community-based intervention trial to eradicate H. pylori is feasible and acceptable. The findings of this trial lead to a distinct evaluation of factors influencing eradication that should be generally considered for future eradication therapies. Trial registration number ChiCTR-TRC-10000979 in accordance with WHO ICTRP requirements. INTRODUCTIONHelicobacter pylori (H. pylori) is a recognised cause of chronic gastritis and peptic ulcer disease, and may play an important role in the etiology of Significance of this studyWhat is already known on this subject?▸ Gastric cancer is a global public health burden, nearly one million new cases are diagnosed each year worldwide, of which 42% cases occur in China. ▸ Helicobacter pylori infection is the main risk factor for gastric cancer, and it was classified as a class I carcinogen for gastric cancer by International Agency for Research on Cancer in 1994. ▸ The Shandong Intervention Trial launched in Linqu in 1995 yielded a 39% reduction in gastric cancer incidence rate after 15 years follow-up. ▸ Benefits and adverse consequences of strategy for gastric cancer prevention by eradication of H. pylori are still in concern in the community setting.What are the new findings?▸ The large community-based intervention trial to eradicate H. pylori is feasible and acceptable in a high-risk area of gastric cancer in China. It gained an elimination of 72.9% of H. pylori in such community intervention trial without severe side effects among all the subjects during the entire 30-month trial pe...

Eradication of Helicobacter pylori has been found to be effective for gastric cancer prevention, but uncertainties remain about the possible adverse consequences such as the potential microbial dysbiosis. In our study, we investigated the association between gut microbiota and H. pylori-related gastric lesions in 47 subjects by deep sequencing of microbial 16S ribosomal RNA (rRNA) gene in fecal samples. The dominant phyla in fecal samples were Bacteroidetes, Firmicutes, and Proteobacteria with average relative abundances of 54.77, 31.37 and 12.91%, respectively. Microbial diversity analysis showed that observed species and Shannon index were increased in subjects with past or current H. pylori infection compared with negative subjects. As for the differential bacteria, the average relative abundance of Bacteroidetes was found to significantly decrease from H. pylori negative (66.16%) to past infection group (33.01%, p = 0.007), as well as from normal (76.49%) to gastritis (56.04%) and metaplasia subjects (46.83%, p = 0.027). For Firmicutes and Proteobacteria, the average relative abundances showed elevated trends in the past H. pylori infection group (47.11, 20.53%) compared to negative group (23.44, 9.05%, p = 0.068 and 0.246, respectively), and similar increased trends were also found from normal (18.23, 5.05%) to gastritis (35.31, 7.23%, p = 0.016 and 0.294, respectively) or metaplasia subjects (32.33, 20.07%, both p < 0.05). These findings suggest that the alterations of fecal microbiota, especially the dominant phyla of Bacteroidetes, Firmicutes and Proteobacteria, may be involved in the process of H. pylori-related gastric lesion progression and provide hints for future evaluation of microbial changes after H. pylori eradication.

Regular consumption of cranberry juice can suppress H. pylori infection in endemically afflicted populations.

Gastric cancer (GC) is a highly aggressive cancer and a major cause of cancer-related deaths worldwide. Approximately half of the world's GC cases and deaths occur in china. GC presents challenges in early diagnosis and effective therapy due to a lack of understanding of the underlying molecular biology. The primary goals of this review are to outline current GC research in china and describe future trends in this field. Areas covered: This review mainly focuses on a series of GC-related advances China has achieved. Considerable progress has been made in understanding the role of H. pylori in GC by a series of population-based studies in well-established high-risk areas; A few germline and somatic alterations have been identified by 'omics' studies; Studies on the mechanisms of malignant phenotypes have helped us to form an in-depth understanding of GC and advance drug discovery. Moreover, identification of potential biomarkers and targeted therapies have facilitated the diagnosis and treatment of GC. However, many challenges remain. Expert commentary: To combat GC, sufficient funding is important. More attention should be paid on early diagnosis and the discovery of novel efficient biomarkers and the development of biomarker-based or targeted therapeutics in GC.