Objective To evaluate the gastric microbiome in patients with chronic superficial gastritis (CSG) and intestinal metaplasia (IM) and investigate the influence of Helicobacter pylori (H. pylori) on the gastric microbiome. Methods Gastric mucosa tissue samples were collected from 54 patients with CSG and IM, and the patients were classified into the following four groups based on the state of H. pylori infection and histology: H. pylori-negative CSG (n=24), H. pylori-positive CSG (n=14), H. pylori-negative IM (n=11), and H. pylori-positive IM (n=5). The gastric microbiome was analyzed by 16S rRNA gene sequencing. Results H. pylori strongly influenced the bacterial abundance and diversity regardless of CSG and IM. In H. pylori-positive subjects, the bacterial abundance and diversity were significantly lower than in H. pylori-negative subjects. The H. pylori-negative groups had similar bacterial composition and bacterial abundance. The H. pylori-positive groups also had similar bacterial composition but different bacterial relative abundance. The relative abundance of Neisseria, Streptococcus, Rothia, and Veillonella were richer in the I-HP group than in G-HP group, especially Neisseria (t=175.1, P<0.001). Conclusions The gastric microbial abundance and diversity are lower in H. pylori- infected patients regardless of CSG and IM. Compared to H. pylori-positive CSG group and H. pylori-positive IM, the relative abundance of Neisseria, Streptococcus, Rothia, and Veillonella is higher in H. pylori-positive patients with IM than in H. pylori-positive patients with CSG, especially Neisseria.
Gastric Mucosa/microbiology* ; Gastritis, Atrophic/microbiology* ; Gastrointestinal Microbiome/genetics* ; Helicobacter Infections/microbiology* ; Helicobacter pylori/genetics* ; Humans ; Metaplasia ; RNA, Ribosomal, 16S/genetics* ; Stomach Neoplasms

OBJECTIVE: To observe the effect of acupuncture at "Baihui" (GV 20), "Zhongwan" (CV 12) and "Zusanli" (ST 36) on intestinal flora in rats with stress gastric ulcer (SGU) , and to explore the mechanism of acupuncture promoting SGU recovery. METHODS: Thirty-one SPF SD rats were randomly divided into a control group (7 rats), a model control group (8 rats), an acupuncture group (8 rats) and a medication group (8 rats). The rats in the model group, acupuncture group and medication group were selected to applied the improved restraint water-immersion stress method to establish the SGU model. After modeling, the rats in the control group and model group were fixed and restrained for 20 min every day for a total of 5 days; the rats in the acupuncture group were intervented with acupuncture at "Baihui" (GV 20), "Zhongwan" (CV 12) and "Zusanli" (ST 36), once a day, 20 min each time, and twisting needle for 30 s every 5 min for a total of 5 days; the rats in the medication group were gavaged by solution of omeprazole enteric-coated tablet (200 mg/mL), 2 mL for each rat, once a day. Guth method was used to calculate the gastric mucosal damage index (GMDI), HE staining was used to observe the pathological changes of gastric mucosa, and 16SrDNA identification was used to detect the structural abundance of intestinal flora. RESULTS: Compared with the control group, the GMDI of rats in the model group was increased (<0.01), the gastric mucosal pathological changes were significant, and the intestinal flora richness index Chao1, Observed species and diversity index Shannon were all decreased (<0.05), the diversity index Simpson was increased (<0.05). Compared with the model group, the GMDI of rats in the acupuncture group and medication group was reduced (<0.01, <0.05), the gastric mucosal damage degree was reduced, and the intestinal flora richness index Chao1, Observed species and diversity index Shannon were all increased (<0.05) and the diversity index Simpson decreased (<0.05). Compared with the medication group, the GMDI of rats in the acupuncture group was reduced (<0.01), the recovery of gastric mucosal injury was better than that of the medication group. CONCLUSION Acupuncture can effectively improve gastric mucosal injury of SGU, and the mechanism may be related to increasing the diversity of intestinal flora and promoting the correction of the disordered intestinal flora.
Acupuncture Points ; Acupuncture Therapy ; Animals ; Gastrointestinal Microbiome ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Stomach Ulcer ; microbiology ; therapy

ObjectiveGastroscopy combined with gastric mucosa biopsies is currently regarded as a gold standard for diagnosis of gastric cancer. However, its application is restricted in clinical practice due to its invasive property. A new noninvasive population screening process combining the assay of anti-Helicobacter pylori antibody and serum pepsinogen (PG) (ABC method) is adopted to recognize the high-risk patients for further endoscopy examination, avoiding the unnecessary gastroscopy for most population and saving the cost consumption for mass screening annually. Nevertheless, controversies exist for the grouping of ABC method and the intervals of gastroscopy surveillance for each group. In this review, we summarized these popular concerned topics for providing useful references to the healthcare practitioner in clinical practice.

Data SourcesThe PubMed databases were systematically searched from the inception dates to November 22, 2017, using the keywords "Helicobacter pylori," "Pepsinogens," and "Stomach Neoplasms."

Study SelectionOriginal articles and reviews on the topics were selected.

ResultsAnti-H. pylori antibody and serum PG concentration showed significant changes under the different status of H. pylori infection and the progression of atrophic gastritis, which can be used for risk stratification of gastric cancer in clinic. In addition, anti-H. pylori antibody titer can be used for further risk stratification of gastric cancer contributing to determine better endoscopy surveillance interval.

ConclusionsThe early detection and diagnosis of gastric cancer benefit from the risk stratification, but the cutoff values for H. pylori antibody and serum PG concentration require further modification.

Antibodies, Bacterial ; blood ; immunology ; Gastroscopy ; Helicobacter Infections ; blood ; immunology ; Helicobacter pylori ; immunology ; Humans ; Mass Screening ; methods ; Stomach Neoplasms ; blood ; microbiology

With the widely application of the metagenomics, the relationship between microbiota and disease has become a hot research topic. Understanding the potential association between upper gastrointestinal cancer or precancerous lesions and microbiota may play an important role in the early detection, clinical diagnosis and treatment, and prognostic evaluation of upper gastrointestinal cancer. Therefore, a literature retrieval was conducted by using PubMed, Embase and wanfang databases to summarize the latest research progress in the microbiota of upper gastrointestinal cancer, including oral, esophageal, gastric cancer and precancerous lesions. Lower microbial diversity or richness in esophageal cancer and precancerous lesions and specific prognostic biomarkers for esophageal cancer were found. Lactobacillus richness showed an increase trend during the process from gastritis to gastric cancer. This paper summarizes the progress in the research of potential biological etiology of upper gastrointestinal cancer from the perspective of metagenomics in order to provide evidence on the, prevention and control of upper gastrointestinal cancer.
Esophageal Neoplasms/microbiology* ; Gastrointestinal Microbiome ; Gastrointestinal Neoplasms/microbiology* ; Gastrointestinal Tract/microbiology* ; Humans ; Lactobacillus ; Metagenomics/trends* ; Microbiota ; Precancerous Conditions/microbiology* ; Prognosis ; Research/trends* ; Risk Factors ; Stomach Neoplasms/microbiology*

BACKGROUND/AIMS: Controversy exists regarding the characteristics of Helicobacter pylori infection-negative gastric cancer (HPIN-GC). The aim of this study was to evaluate clinicopathologic features of HPIN-GC compared to H. pylori infection-positive gastric cancer (HPIP-GC) using a comprehensive analysis that included genetic and environmental factors. METHODS: H. pylori infection status of 705 resectable gastric cancer patients was determined by the rapid urease test, testing for anti-H. pylori antibodies, histologic analysis and culture of gastric cancer tissue samples, and history of H. pylori eradication. HPIN-GC was defined as gastric cancer that was negative for H. pylori infection based on all five methods and that had no evidence of atrophy in histology or serology. RESULTS: The prevalence of HPIN-GC was 4% (28/705). No significant differences with respect to age, sex, smoking, drinking, family history of gastric cancer or obesity were observed between the two groups. HPIN-GC tumors were marginally more likely to involve the cardia (14.3% for HPIN-GC vs 5.3% for HPIP-GC, p=0.068). The Lauren classification, histology, and TNM stage did not differ according to H. pylori infection status. Microsatellite instability was not different between the two groups, but p53 overexpression in HPIN-GC was marginally higher than in HPIP-GC (56.0% for HPIN-GC vs 37.0% for HPIP-GC, p=0.055). CONCLUSIONS: The prevalence of HPIN-GC was extremely low, and its clinicopathologic characteristics were similar to HPIP-GC.
Antibodies, Bacterial/analysis ; Female ; Helicobacter Infections/*complications/epidemiology/microbiology ; *Helicobacter pylori ; Humans ; Male ; Middle Aged ; Prevalence ; Prospective Studies ; Republic of Korea/epidemiology ; Stomach Neoplasms/epidemiology/*microbiology/*pathology/surgery ; Urease/analysis

Gastric dysplasia is a neoplastic lesion and a precursor of gastric cancer. The Padova, Vienna, and World Health Organization classifications were developed to overcome the discrepancies between Western and Japanese pathologic diagnoses and to provide a universally accepted classification of gastric epithelial neoplasia. At present, the natural history of gastric dysplasia is unclear. Much evidence suggests that patients with high-grade dysplasia are at high risk of progression to carcinoma or synchronous carcinoma. Therefore, endoscopic resection is required. Although patients with low-grade dysplasia have been reported to be at low risk of progression to carcinoma, due to the marked histologic discrepancies between forceps biopsy and endoscopic specimens, endoscopic resection for this lesion is recommended, particularly in the presence of other risk factors (large size; depressed gross type; surface erythema, unevenness, ulcer, or erosion; and tubulovillous or villous histology). Helicobacter pylori eradication in patients with dysplasia after endoscopic resection appear to reduce the incidence of metachronous lesions.
Anti-Bacterial Agents/therapeutic use ; Biopsy ; Carcinoma in Situ/classification/microbiology/*pathology/*surgery ; Disease Progression ; *Gastrectomy/adverse effects/methods ; Gastric Mucosa/microbiology/*pathology/*surgery ; Gastroscopy ; Helicobacter Infections/drug therapy/microbiology ; Helicobacter pylori/drug effects ; Humans ; Neoplasm Grading ; Precancerous Conditions/classification/microbiology/*pathology/*surgery ; Predictive Value of Tests ; Risk Factors ; Stomach Neoplasms/classification/microbiology/*pathology/*surgery ; Treatment Outcome

Although the age-adjusted incidence of gastric cancer is declining, the absolute number of new cases of gastric cancer is increasing due to population growth and aging. An effective strategy is needed to prevent this deadly cancer. Among the available strategies, screen-and-treat for Helicobacter pylori infection appears to be the best approach to decrease cancer risk; however, implementation of this strategy on the population level requires a systematic approach. The program also must be integrated into national healthcare priorities to allow the limited resources to be most effectively allocated. Implementation will require adoption of an appropriate screening strategy, an efficient delivery system with a timely referral for a positive test, and standardized treatment regimens based on clinical efficacy, side effects, simplicity, duration, and cost. Within the population, there are subpopulations that vary in risk such that a "one size fits all" approach is unlikely to be ideal. Sensitivity analyses will be required to identify whether the programs can be utilized by heterogeneous populations and will likely require adjustments to accommodate the needs of subpopulations.
Health Priorities ; Helicobacter Infections/complications/diagnosis/microbiology/*therapy ; Helicobacter pylori ; Humans ; Mass Screening ; Stomach Neoplasms/microbiology/*prevention & control

The epithelial cytokine response, associated with reactive oxygen species (ROS), is important in Helicobacter pylori (H. pylori)-induced inflammation. H. pylori induces the production of ROS, which may be involved in the activation of mitogen-activated protein kinases (MAPK), janus kinase/signal transducers and activators of transcription (Jak/Stat), and oxidant-sensitive transcription factor, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB), and thus, expression of interleukin-8 (IL-8) in gastric epithelial cells. alpha-lipoic acid, a naturally occurring thiol compound, is a potential antioxidant. It shows beneficial effects in treatment of oxidant-associated diseases including diabetes. The present study is purposed to investigate whether alpha-lipoic acid inhibits expression of inflammatory cytokine IL-8 by suppressing activation of MAPK, Jak/Stat, and NF-kappaB in H. pylori-infected gastric epithelial cells. Gastric epithelial AGS cells were pretreated with or without alpha-lipoic acid for 2 h and infected with H. pylori in a Korean isolate (HP99) at a ratio of 300:1. IL-8 mRNA expression was analyzed by RT-PCR analysis. IL-8 levels in the medium were determined by enzyme-linked immunosorbent assay. NF-kappaB-DNA binding activity was determined by electrophoretic mobility shift assay. Phospho-specific and total forms of MAPK and Jak/Stat were assessed by Western blot analysis. ROS levels were determined using dichlorofluorescein fluorescence. As a result, H. pylori induced increases in ROS levels, mRNA, and protein levels of IL-8, as well as the activation of MAPK [extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun NH2-terminal kinase 1/2 (JNK1/2), p38], Jak/Stat (Jak1/2, Stat3), and NF-kappaB in AGS cells, which was inhibited by alpha-lipoic acid. In conclusion, alpha-lipoic acid may be beneficial for prevention and/or treatment of H. pylori infection-associated gastric inflammation.
Enzyme-Linked Immunosorbent Assay ; Epithelial Cells/metabolism ; Gastric Mucosa/*drug effects/metabolism/microbiology ; Gene Expression Regulation, Bacterial ; Helicobacter Infections/immunology/*metabolism ; Helicobacter pylori/drug effects/*pathogenicity ; Humans ; Interleukin-8/genetics/*metabolism ; JNK Mitogen-Activated Protein Kinases ; Janus Kinase 1 ; Mitogen-Activated Protein Kinases/*biosynthesis ; NF-kappa B/*metabolism ; RNA, Messenger/isolation & purification/metabolism ; Reactive Oxygen Species/metabolism ; STAT3 Transcription Factor ; Stomach/metabolism/*microbiology ; Thioctic Acid/*pharmacology

BACKGROUND/AIMS: Helicobacter pylori cytotoxin-associated gene A (CagA) has been suggested to be involved in the inactivation of Runt-related transcription factor 3 (RUNX3), a known gastric carcinoma tumor suppressor gene. It remains unclear how H. pylori CagA initiates or maintains RUNX3 promoter methylation and inactivates its protein expression in gastric carcinoma. METHODS: RUNX3 promoter methylation status, RUNX3 expression, and H. pylori CagA were investigated in 76 sample pairs of gastric carcinoma tissue. The patients' medical records were reviewed. The association between RUNX3 methylation or loss of RUNX3 expression and clinicopathologic variables according to H. pylori CagA status were investigated. RESULTS: In gastric carcinoma patients with H. pylori CagA-positive infection, RUNX3 methylation did not show association with lymphatic invasion, venous invasion, and TNM stages. However RUNX3 methylation was observed more frequently in poorly differentiated adenocarcinoma and signet ring cell carcinoma (77.8% vs. 20.0%, p=0.023) in early stage. In gastric carcinoma patients with H. pylori CagA-positive infection, loss of RUNX3 expression did not show association with lymphatic invasion, venous invasion, and TNM stages. However loss of RUNX3 expression was observed more frequently in early gastric carcinoma than in advanced gastric carcinoma (84.2% vs. 75.0%, p=0.51), but this difference was not significant. CONCLUSIONS: In gastric carcinoma patients with H. pylori CagA-positive infection, RUNX3 methylation or loss of RUNX3 expression did not show correlation with lymphovascular invasion and TNM stages. In early gastric carcinoma patients with H. pylori CagA-positive infection, RUNX3 methylation was observed more in poorly differentiated adenocarcinoma and signet ring cell carcinoma.
Adult ; Aged ; Aged, 80 and over ; Antigens, Bacterial/*metabolism ; Bacterial Proteins/*metabolism ; Cell Line, Tumor ; Core Binding Factor Alpha 3 Subunit/genetics/*metabolism ; Female ; *Gene Expression Regulation, Neoplastic ; Helicobacter Infections/complications/microbiology ; Helicobacter pylori/isolation & purification/*metabolism ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Methylation ; Middle Aged ; Neoplasm Staging ; Promoter Regions, Genetic ; Retrospective Studies ; Stomach Neoplasms/complications/microbiology/*pathology

Most gastric cancers are caused by infection with the common human bacterial pathogen, Helicobacter pylori. It is now accepted that gastric cancer can be prevented and virtually eliminated by H. pylori eradication and this knowledge was responsible for country-wide H. pylori eradication combined with secondary cancer prevention for those with residual risk that was introduced in Japan in 2013. Korea is a high H. pylori prevalence and high gastric cancer incidence country and a good candidate for a gastric cancer elimination program. The presence of an H. pylori infection is now considered as an indication for treatment of the infection. However, antimicrobial drug resistance is common among H. pylori in Korea making effective therapy problematic. Country-wide studies of the local and regional antimicrobial resistance patterns are needed to choose the most appropriate therapies. H. pylori and gastric cancer eradication can be both efficient and cost effective making it possible and practical to make Korea H. pylori and gastric cancer free. There is no reason to delay.
Anti-Bacterial Agents/*therapeutic use ; Disease Eradication ; Drug Resistance, Bacterial ; Helicobacter Infections/*drug therapy/epidemiology/microbiology ; Helicobacter pylori/*drug effects/growth & development ; Humans ; Prevalence ; Primary Prevention/*methods ; Republic of Korea/epidemiology ; Risk Assessment ; Risk Factors ; Stomach Neoplasms/epidemiology/microbiology/*prevention & control ; Treatment Outcome