Kyoto classification of gastritis: Advances and future perspectives in endoscopic diagnosis of gastritis

This editorial provides an update of the recent evidence on the endoscopy-based Kyoto classification of gastritis, clarifying the shortcomings of the Kyoto classification, and providing prospects for future research, with particular focus on the histological subtypes of gastric cancer (GC) and Helicobacter pylori (H. pylori) infection status. The total Kyoto score is designed to express GC risk on a score ranging from 0 to 8, based on the following five endoscopic findings: Atrophy, intestinal metaplasia (IM), enlarged folds (EF), nodularity, and diffuse redness (DR). The total Kyoto score reflects H. pylori status as follows: 0, ≥ 2, and ≥ 4 indicate a normal stomach, H. pylori-infected gastritis, and gastritis at risk for GC, respectively. Regular arrangement of collecting venules (RAC) predicts non-infection; EF, nodularity, and DR predict current infection; map-like redness (MLR) predicts past infection; and atrophy and IM predict current or past infection. Atrophy, IM, and EF all increase the incidence of H. pylori-infected GC. MLR is a specific risk factor for H. pylori-eradicated GC, while RAC results in less GC. Diffuse-type GC can be induced by active inflammation, which presents as EF, nodularity, and atrophy on endoscopy, as well as neutrophil and mononuclear cell infiltration on histology. In contrast, intestinal-type GC develops via atrophy and IM, and is consistent between endoscopy and histology. However, this GC risk-scoring design needs to be improved.     

Surveillance strategies for precancerous gastric conditions after Helicobacter pylori eradication: There is still need for a tailored approach

Prevailing evidence declares that Helicobacter pylori (H. pylori) eradication therapy could shift precancerous gastric conditions (PGC) and positively confines gastric cancer (GC) risk during long-term endoscopic follow-up. Nonetheless, there is a yet unsolved controversy regarding the best-individualized surveillance strategies following H. pylori eradication, based on malignant risk stratification. This last dispute is due to the uncertainty of contemporary evidence and the role of H. pylori inflammatory changes in underestimating PGC at the index endoscopy. However, the current state of the art suggests that it is reasonable that high-quality endoscopy with histological assessment for the most accurate diagnosis of PGC may be delayed in selected high-risk patients without alarm signs for malignancy, following the eradication of H. pylori. Notwithstanding, these aspects need to be further examined in the next future to establish and optimize the most beneficial and cost-effective strategies for recognizing and managing H. pylori-positive patients with PGC in the short- and long-term follow-up. Accordingly, additional studies are yet required to sharpen the hazard stratification of patients with the greatest chance of GC evolution, also recognizing the evolving racial, ethnic, immigration factors and the necessity of novel biomarkers to limit GC development or accomplish a diagnosis of malignancy at an early stage.     

The association between CagA status and the development of esophagitis after the eradication of Helicobacter pylori

BACKGROUND: Strains of Helicobacter pylori with the cytotoxine-associated gene A (cagA) are linked to severe forms of gastroduodenal disease. Although eradication of H. pylori may predispose to the development of reflux esophagitis, the effects of CagA status on risk of esophagitis after successful H. pylori treatment are not known.

METHODS: We studied 50 consecutive patients without esophagitis in whom H. pylori was eradicated successfully. CagA status was determined by immunoblotting sera from patients against H. pylori antigens. Patients underwent upper gastrointestinal endoscopy before eradication and 6, 12, 18, and 24 months after eradication or when reflux symptoms occurred. Biopsy specimens of the antrum and corpus were evaluated for gastritis before H. pylori eradication and at the end of the study. The sum of the scores for acute and chronic inflammation (both measured on a 0 [absent] to 3 [severe] scale) comprised the total gastritis severity score.

RESULTS: In a multivariate proportional hazards regression analysis, positive CagA serology (hazard ratio [HR] = 10, 95% confidence interval [CI]: 1.3 to 81) and moderate-to-severe corpus gastritis (total severity score ≥4) before eradication (HR = 2.3, 95% CI: 1.2 to 6.1) were independent risk factors for the development of esophagitis after H. pylori eradication.

CONCLUSION: Patients infected with strains of H. pylori that are cagA-positive are at increased risk of developing esophagitis after eradication of H. pylori.     

Increased expression of matrix metalloproteinase-9 associated with gastric ulcer recurrence

AIM: To compare matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)-1 in gastric ulcer (GU) and chronic superficial gastritis (CSG). METHODS: This study enrolled 63 patients with GU and 25 patients with CSG. During upper gastroduodenal endoscopy, we took samples of gastric mucosa from the antrum and ulcer site from patients with GU, and samples of antral mucosa from patients with CSG. Mucosal biopsy tissues were cultured for 24 h, and the culture supernatant was measured for levels of MMP-9 and TIMP-1. After receiving eradication therapy for Helicobacter pylori (H. pylori ) and 8 wk proton-pump inhibitor therapy for GU, follow-up endoscopy examination was performed after 6 mo and whenever severe symptoms occurred. RESULTS: Levels of MMP-9 and TIMP-1 at the ulcer site or in the antrum were significantly higher in GU than CSG patients. MMP-9 levels at the ulcer site were significantly higher than in the antrum in GU patients, and had a significantly positive correlation with TIMP-1. MMP-9 levels were significantly higher in H. pylori -positive than H. pylori -negative GU and CSG patients. Levels of MMP-9 or TIMP-1 at the ulcer site were associated with the histological severity of activity and inflammation. About 57 GU patients were followed up, and seven had GU recurrence. H. pyloriinfection and MMP-9 levels were risk factors for the recurrence of GU adjusted for age and sex by multiple logistic regression analysis. CONCLUSION: MMP-9 may perform an important function in gastric ulcer formation and recurrence.     

Standard vs magnifying narrow-band imaging endoscopy for diagnosis of Helicobacter pylori infection and gastric precancerous conditions

BACKGROUNDAdvances in endoscopic imaging enable the identification of patients at high risk of gastric cancer. However, there are no comparative data on the utility of standard and magnifying narrow-band imaging (M-NBI) endoscopy for diagnosing Helicobacter pylori (H. pylori) infection, gastric atrophy, and intestinal metaplasia. AIMTo compare the diagnostic performance of standard and M-NBI endoscopy for H. pylori gastritis and precancerous conditions. METHODSIn 254 patients, standard endoscopy findings were classified into mosaic-like appearance (type A), diffuse homogenous redness (type B), and irregular redness with groove (type C). Gastric mucosal patterns visualized by M-NBI were classified as regular round pits with polygonal sulci (type Z-1), more dilated and linear pits without sulci (type Z-2), and loss of gastric pits with coiled vessels (type Z-3). RESULTSThe diagnostic accuracy of standard and M-NBI endoscopy for H. pylori gastritis was 93.3% and 96.1%, respectively. Regarding gastric precancerous conditions, the accuracy of standard and M-NBI endoscopy was 72.0% vs 72.6% for moderate to severe atrophy, and 61.7% vs. 61.1% for intestinal metaplasia in the corpus, respectively. Compared to type A and Z-1, types B+C and Z-2+Z-3 were significantly associated with moderate to severe atrophy [odds ratio (OR) = 5.56 and 8.67] and serum pepsinogen I/II ratio of ≤ 3 (OR = 4.48 and 5.69). CONCLUSIONClose observation of the gastric mucosa by standard and M-NBI endoscopy is useful for the diagnosis of H. pylori gastritis and precancerous conditions.     

Prevalence of Helicobacter pylori infection and atrophic gastritis in patients with dyspeptic symptoms in Myanmar

AIM: To survey the detailed analyses for Helicobacter pylori(H. pylori) infection and gastric mucosal status in Myanmar.METHODS: A total of 252 volunteers with dyspeptic symptoms(155 female and 97 male; mean age of 43.6 ± 14.2 years) was participated in Yangon and Mandalay. The status of H. pylori infection was determined based on 5 different tests including rapid urease test, culture, histology, immunohistochemistry and serology. Histological scores were evaluated according to the update Sydney system and the Operative Link for Gastritis Assessment system. Pepsinogen(PG)Ⅰand PG Ⅱ were measured using enzyme-linked immunosorbent assays.RESULTS: The overall prevalence of H. pylori infectionwas 48.0%. There was no relationship between age and infection rate. Even in young group(less than 29 years old), the H. pylori infection rate was relatively high(41.9%). The prevalence of H. pylori infection was significantly higher in Yangon than that of Mandalay. H. pylori infection was significantly associated with the presence of gastric mucosal atrophy. All 7 subjects with peptic ulcer were infected with H. pylori. Although H. pylori-positive subjects showed stronger gastritis than H. pylori-negative subjects, most cases had mild gastritis.CONCLUSION: We revealed the prevalence of H. pylori infection in patients with dyspeptic symptoms in Myanmar. The H. pylori infection was a risk factor for peptic ulcer and stronger gastritis.     

Extremely high prevalence of Helicobacter pylori infection in Bhutan

AIM: To revealed the prevalence of Helicobacter pylori (H. pylori ) infection in the Bhutanese population. METHODS: We recruited a total of 372 volunteers (214 females and 158 males; mean age of 39.6 ± 14.9 years) from three Bhutanese cities (Thimphu, Punaka, and Wangdue). The status of H. pylori infection was determined based on five different tests: the rapid urease test (CLO test), culture, histology, immunohistochemistry (IHC), and serum anti H. pylori -antibody. RESULTS: The serological test showed a significantly higher positive rate compared with the CLO test, culture, histology and IHC (P < 0.001, P < 0.001, P=0.01, and P=0.01, respectively). When the subjects were considered to be H. pylori positive in the case of at least one test showing a positive result, the overall prevalence of H. pylori infection in Bhutan was 73.4%. The prevalence of H. pylori infection significantly decreased with age (P < 0.01). The prevalence of H. pylori infection was lower in Thimphu than in Punakha and Wangdue (P=0.001 and 0.06, respectively). The prevalence of H. pylori infection was significantly higher in patients with peptic ulcers than in those with gastritis (91.4% vs 71.3%, P=0.003). CONCLUSION: The high incidence of gastric cancer in Bhutan may be attributed to the high prevalence of H. pylori infection.     

Progress in elucidating the relationship between Helicobacter pylori infection and intestinal diseases

Helicobacter pylori (H. pylori) infection causes changes to the intestinal flora, such as small intestinal bacterial overgrowth, and increases gastric acid secretion-stimulating gastrointestinal hormones, mainly gastrin, due to a decrease in gastric acid caused by atrophic gastritis. In addition, the cellular components of H. pylori travel through the intestinal tract, so the bacterial infection affects the immune system. Therefore, the effects of H. pylori infection are observed not only in the stomach and the proximal duodenum but also in the small and large intestines. In particular, meta-analyses reported that H. pylori-infected individuals had an increased risk of colorectal adenoma and colorectal cancer. Moreover, a recent study reported that the risk of developing colorectal cancer was increased in subjects carrying H. pylori vacuolating cytotoxin A antibody. In addition, it has been reported that H. pylori infection exacerbates the symptoms of Fabry’s disease and familial Mediterranean fever attack and is involved in irritable bowel syndrome and small intestinal ulcers. On the other hand, some studies have reported that the frequency of ulcerative colitis, Crohn’s disease, and celiac disease is low in H. pylori-infected individuals. Thus, H. pylori infection is considered to have various effects on the small and large intestines. However, few studies have reported on these issues, and the details of their effects have not been well elucidated. Therefore, additional studies are needed.     

窄带成像内镜诊断慢性萎缩性胃炎的临床价值

目的探讨窄带成像（narrow-bandimaging,NBI）内镜诊断慢性萎缩性胃炎的临床价值。方法选取78例临床疑诊慢性萎缩性胃炎的患者依次进行普通内镜、NBI及病理学检查,并进行比较。结果在NBI模式下,对慢性萎缩性胃炎诊断的敏感性、特异性、阳性预测值、阴性预测值分别为73.842%、84.61%、96.00%、39.29%。远高于普通内镜组的49.23%、61.53%、86.49%、19.51%;在NBI组48例阳性病例中,伴肠化生17例,伴轻度异型增生19例,伴重度异型增生3例,亦显著高于普通内镜组的6、8、1例（P〈0.05）。结论 NBI可明显提高诊断慢性萎缩性胃炎的准确率,且操作简便、快捷。     

Does the antibody production ability affect the serum anti-Helicobacter pylori IgG titer?

AIM: To investigate the relationship between serum titers of anti-Helicobacter pylori(H.pylori) immunoglobulin G(IgG) and hepatitis B virus surface antibody(HBsA b).METHODS: Korean adults were included whose samples had positive Giemsa staining on endoscopic biopsy and were studied in the hepatitis B virus surface antigen(HBsA g)/HBsA b serologic assay,pepsinogen(PG) assay,and H.pylori serologic test on the same day.Subjects were excluded if they were positive for HBs Ag,had a recent history of medication,or had other medical condition(s).We analyzed the effects of the following factors on serum titers of HBsA b and the anti-H.pylori IgG : Age,density of H.pylori infiltration in biopsy samples,serum concentrations of PG Ⅰ and PG Ⅱ,PG Ⅰ/Ⅱ ratio,and white blood cell count.RESULTS: Of 111 included subjects,74(66.7%) exhibited a positive HBsA b finding.The serum anti-H.pylori IgG titer did not correlate with the serum HBsA b titer(P = 0.185); however,it correlated with the degree of H.pylori infiltration on gastric biopsy(P 0.001) and serum PG Ⅱ concentration(P = 0.042).According to the density of H.pylori infiltration on gastric biopsy,subjects could be subdivided into those with a marked(median: 3.95,range 0.82-4.00)(P = 0.458),moderate(median: 3.37,range 1.86-4.00),and mild H.pylori infiltrations(median: 2.39,range 0.36-4.00)(P 0.001).Subjects with a marked H.pylori infiltration on gastric biopsy had the highest serological titer,whereas in subjects with moderate and mild H.pylori infiltrations titers were correspondingly lower(P 0.001).After the successful eradication,significant decreases of the degree of H.pylori infiltration(P 0.001),serum anti-H.pylori IgG titer(P 0.001),and serum concentrations of PG I(P = 0.028) and PG Ⅱ(P = 0.028) were observed.CONCLUSION: The anti-H.pylori IgG assay can be used to estimate the burden of bacteria in immunocompetent hosts with H.pylori infection,regardless of the HBsA b titer after HBV vaccination.     

Microbiota in the stomach and application of probiotics to gastroduodenal diseases

The stomach is a hostile environment for most microbes because strong gastric acid kills indigenous microorganisms. Thus, the mass of indigenous microbes detected by traditional culturing method in a highly acidic stomach is reported to be very small. However, in a stomach with less acidity due to atrophic changes of the gastric mucosa, the number of live gastric microbiota dramatically increases and their composition changes. A probiotic is defined as a live microorganism that, when administered in adequate amounts, confers a health benefit on the host. The administration of probiotics to the stomach has thus far been considered impractical, mainly due to the strong acidity in the stomach. The identification of candidate probiotic strains with sufficient resistance to acidity and the ability to achieve close proximity to the gastric mucosa could enable the application of probiotics to the stomach. The utilization of probiotics alone for Helicobacter pylori (H. pylori) infection significantly improves gastric mucosal inflammation and decreases the density of H. pylori on the mucosa, although complete eradication of H. pylori has not yet been demonstrated. The use of probiotics in combination with antimicrobial agents significantly increases the H. pylori eradication rate, especially when the H. pylori strains are resistant to antimicrobial agents. While H. pylori has been considered the most important pathogenic bacterium for the development of gastric cancer, bacteria other than H. pylori are also suggested to be causative pathogens that promote the development of gastric cancer, even after the eradication of H. pylori. Increased non-H. pylori Gram-negative bacteria in the stomach with weak acidity accompanying atrophic gastritis may perpetuate gastric mucosal inflammation and accelerate carcinogenic progression, even after H. pylori eradication. Probiotics restore the acidity in this stomach environment and may therefore prevent the development of gastric cancer by termination of Gram-negative bacteria-induced inflammation. Functional dyspepsia (FD) is defined as the presence of symptoms that are thought to originate in the gastroduodenal region in the absence of any organic, systematic or metabolic diseases. Accumulating evidence has pointed out the duodenum as a target region underlying the pathophysiology of FD. A randomized placebo-controlled clinical trial using a probiotic strain (LG21) demonstrated a significant improving effect on major FD symptoms. One of the possible mechanisms of this effect is protection of the duodenal mucosa from injurious intestinal bacteria through the resolution of small intestinal bacterial over growth.     

Could microbiome analysis be a new diagnostic tool in gastric carcinogenesis for high risk,Helicobacter pylori negative patients?

Helicobacter pylori (H. pylori) has long been believed to be the major colonizer of the stomach, but recent advances in genetic sequencing have allowed for further differentiation of the gastric microbiome and revealed the true complexity of the gastric microbiome. One of the few studies specifically evaluated the microbiome in the H. pylori negative patient population. They concluded that various stages of gastric carcinogenesis are associated with distinct bacterial taxa that could service both a predictive and diagnostic purpose. While the study has some limitations, the conclusions they make are intriguing and should prompt a larger prospective study to be done that spans multiple geographic regions.     

NBI放大内镜在胃黏膜糜烂鉴别诊断中的价值

目的探讨NBI放大内镜在胃黏膜糜烂鉴别诊断中的价值,以及在胃黏膜癌前病变中的诊断价值。方法应用NBI电子放大内镜,对310例患者的胃黏膜糜烂灶进行细微结构形态学观察,并与观察部位活检所得的病理组织学改变进行比较分析。结果胃黏膜糜烂灶处胃小凹形态未见到A型、B型者;365处C型中组织病理均为慢性活动性浅表性炎症;160处D型中,92.5%（148/160）为萎缩性炎症;65处E型中,86.15%（56/65）为肠上皮化生;35处F型中,91.42%（32/35）为异型增生,8.57%（3/30）为肠上皮化生。59例肠上皮化生未发现明显异常增生的毛细血管,而32例异型增生的F型黏膜表面。90.63%（29/32）呈现出不同程度异常增生的毛细血管。与病理组织学比较,NBI放大内镜观察胃黏膜糜烂小凹形态与病理组织学改变呈显著正相关（P〈0.01）。结论 NBI放大内镜在胃黏膜糜烂灶性质的判断中有很高的临床应用价值,可应用于胃黏膜癌前病变的普查。     

Hematologic manifestations of Helicobacter pylori infection

Helicobacter pylori (H. pylori) is the most common infection in humans, with a marked disparity between developed and developing countries. Although H. pylori infections are asymptomatic in most infected individuals, they are intimately related to malignant gastric conditions such as gastric cancer and gastric mucosa-associated lymphoid tissue (MALT) lymphoma and to benign diseases such as gastritis and duodenal and gastric peptic ulcers. Since it was learned that bacteria could colonize the gastric mucosa, there have been reports in the medical literature of over 50 extragastric manifestations involving a variety medical areas of specialization. These areas include cardiology, dermatology, endocrinology, gynecology and obstetrics, hematology, pneumology, odontology, ophthalmology, otorhinolaryngology and pediatrics, and they encompass conditions with a range of clear evidence between the H. pylori infection and development of the disease. This literature review covers extragastric manifestations of H. pylori infection in the hematology field. It focuses on conditions that are included in international consensus and management guides for H. pylori infection, specifically iron deficiency, vitamin B₁₂ (cobalamin) deficiency, immune thrombocytopenia, and MALT lymphoma. In addition, there is discussion of other conditions that are not included in international consensus and management guides on H. pylori, including auto-immune neutropenia, antiphospholipid syndrome, plasma cell dyscrasias, and other hematologic diseases.     

DNA diagnostics for reliable and universal identification of Helicobacter pylori

Reliable diagnostics are a major challenge for the detection and treatment of Helicobacter pylori (H. pylori) infection. Currently at the forefront are non-invasive urea breath test (UBT) and stool antigen test (SAT). Polymerase chain reaction (PCR) is not endorsed due to nonspecific primers and the threat of false-positives. The specificity of DNA amplification can be achieved by nested PCR (NPCR), which involves two rounds of PCR. If the primers are properly designed for the variable regions of the 16S rRNA gene, it is not difficult to develop an NPCR assay for the unambiguous identification of H. pylori. Elaborate NPCR for a 454 bp amplicon was validated on 81 clinical biopsy, stool, and saliva samples, each from the same individuals, and compared with available H. pylori assays, namely histology, rapid urease test, SAT, and ¹³C-UBT. The assay was much more sensitive than simple PCR, and it was equally sensitive in biopsy samples as the ¹³C-UBT test, which is considered the gold standard. In addition, it is sufficiently specific because sequencing of the PCR products exclusively confirmed the presence of H. pylori-specific DNA. However, due to the threshold and lower abundance, the sensitivity was much lower in amplifications from stool or saliva. Reliable detection in saliva also complicates the ability of H. pylori to survive in the oral cavity aside from and independent of the stomach. The reason for the lower sensitivity in stool is DNA degradation; therefore, a new NPCR assay was developed to obtain a shorter 148 bp 16S rRNA amplicon. The assay was validated on stool samples from 208 gastroenterological patients and compared to SAT results. Surprisingly, this NPCR revealed the presence of H. pylori in twice the number of samples as SAT, indicating that many patients are misdiagnosed, not treated by antibiotics, and their problems are interpreted as chronic. Thus, it is unclear how to properly diagnose H. pylori in practice. In the first approach, SAT or UBT is sufficient. If samples are negative, the 148 bp amplicon NPCR assay should be performed. If problems persist, patients should not be considered negative, but due to threshold H. pylori abundance, they should be periodically tested. The advantage of NPCR over UBT is that it can be used universally, including questionable samples taken from patients with achlorhydria, receiving proton pump inhibitors, antibiotics, bismuth compound, intestinal metaplasia, or gastric ulcer bleeding.     

Gastrointestinal microbiome and Helicobacter pylori:Eradicate,leave it as it is,or take a personalized benefit-risk approach?

Helicobacter pylori(H.pylori)is generally regarded as a human pathogen and a class 1 carcinogen,etiologically related to gastric and duodenal ulcers,gastric cancer,and mucosa-associated lymphoid tissue lymphoma.However,H.pylori can also be regarded as a commensal symbiont.Unlike other pathogenic/opportunistic bacteria,H.pylori colonization in infancy is facilitated by T helper type 2 immunity and leads to the development of immune tolerance.Fucosylated gastric mucin glycans,which are an important part of the innate and adaptive immune system,mediate the adhesion of H.pylori to the surface of the gastric epithelium,contributing to successful colonization.H.pylori may have beneficial effects on the host by regulating gastrointestinal(GI)microbiota and protecting against some allergic and autoimmune disorders and inflammatory bowel disease.The potential protective role against inflammatory bowel disease may be related to both modulation of the gut microbiota and the immunomodulatory properties of H.pylori.The inverse association between H.pylori and some potentially proinflammatory and/or procarcinogenic bacteria may suggest it regulates the GI microbiota.Eradication of H.pylori can cause various adverse effects and alter the GI microbiota,leading to short-term or long-term dysbiosis.Overall,studies have shown that gastric Actinobacteria decrease after H.pylori eradication,Proteobacteria increase during short-term follow-up and then return to baseline levels,and Enterobacteriaceae and Enterococcus increase in the short-term and interim follow-up.Various gastric mucosal bacteria(Actinomyces,Granulicatella,Parvimonas,Peptostreptococcus,Prevotella,Rothia,Streptococcus,Rhodococcus,and Lactobacillus)may contribute to precancerous gastric lesions and cancer itself after H.pylori eradication.H.pylori eradication can also lead to dysbiosis of the gut microbiota,with increased Proteobacteria and decreased Bacteroidetes and Actinobacteria.The increase in gut Proteobacteria may contribute to adverse effects during and after eradication.The decrease in Actinobacteria,which are pivotal in the maintenance of gut homeostasis,can persist for>6 mo after H.pylori eradication.Furthermore,H.pylori eradication can alter the metabolism of gastric and intestinal bacteria.Given the available data,eradication cannot be an unconditional recommendation in every case of H.pylori infection,and the decision to eradicate H.pylori should be based on an assessment of the benefit-risk ratio for the individual patient.Thus,the current guidelines based on the unconditional"test-and-treat"strategy should be revised.The most cautious and careful approach should be taken in elderly patients with multiple eradication failures since repeated eradication can cause antibiotic-associated diarrhea,including severe Clostridioides difficile-associated diarrhea and colitis and antibiotic-associated hemorrhagic colitis due to Klebsiella oxytoca.Furthermore,since eradication therapy with antibiotics and proton pump inhibitors can lead to serious adverse effects and/or dysbiosis of the GI microbiota,supplementation of probiotics,prebiotics,and microbial metabolites(e.g.,butyrate+inulin)should be considered to decrease the negative effects of eradication.     

Beyond the stomach: An updated view of Helicobacter pylori pathogenesis,diagnosis, and treatment

Helicobacter pylori (H. pylori) is an extremely common, yet underappreciated, pathogen that is able to alter host physiology and subvert the host immune response, allowing it to persist for the life of the host. H. pylori is the primary cause of peptic ulcers and gastric cancer. In the United States, the annual cost associated with peptic ulcer disease is estimated to be $6 billion and gastric cancer kills over 700000 people per year globally. The prevalence of H. pylori infection remains high (> 50%) in much of the world, although the infection rates are dropping in some developed nations. The drop in H. pylori prevalence could be a double-edged sword, reducing the incidence of gastric diseases while increasing the risk of allergies and esophageal diseases. The list of diseases potentially caused by H. pylori continues to grow; however, mechanistic explanations of how H. pylori could contribute to extragastric diseases lag far behind clinical studies. A number of host factors and H. pylori virulence factors act in concert to determine which individuals are at the highest risk of disease. These include bacterial cytotoxins and polymorphisms in host genes responsible for directing the immune response. This review discusses the latest advances in H. pylori pathogenesis, diagnosis, and treatment. Up-to-date information on correlations between H. pylori and extragastric diseases is also provided.     

Impact of Helicobacter pylori infection on gut microbiota

A number of studies have revealed the association between Helicobacter pylori (H. pylori) infection and the gut microbiota. More than half of the investigations on the impact of H. pylori on the gut microbiota have been the sub-analyses of the influence of eradication therapy. It was observed that H. pylori eradication altered gut microbiota within a short period after eradication, and majority of the alterations took a long period of time to reverse back to the original. Changes in the gut microbiota within a short period after eradication may be attributed to antibiotics and proton pump inhibitors. Modification of gastric acidity in the stomach caused by a long-term H. pylori infection alters the gut microbiota. Analysis of the gut microbiota should be conducted in a large population, adjusting for considerable biases associated with the composition of the gut microbiota, such as age, sex, body mass index, diet and the virulence of H. pylori.     

Development of Epstein-Barr virus-associated gastric cancer: Infection,inflammation, and oncogenesis

Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) cells originate from a single-cell clone infected with EBV. However, more than 95% of patients with gastric cancer have a history of Helicobacter pylori (H. pylori) infection, and H. pylori is a major causative agent of gastric cancer. Therefore, it has long been argued that H. pylori infection may affect the development of EBVaGC, a subtype of gastric cancer. Atrophic gastrointestinal inflammation, a symptom of H. pylori infection, is observed in the gastric mucosa of EBVaGC. Therefore, it remains unclear whether H. pylori infection is a cofactor for gastric carcinogenesis caused by EBV infection or whether H. pylori and EBV infections act independently on gastric cancer formation. It has been reported that EBV infection assists in the onco-genesis of gastric cancer caused by H. pylori infection. In contrast, several studies have reported that H. pylori infection accelerates tumorigenesis initiated by EBV infection. By reviewing both clinical epidemiological and experimental data, we reorganized the role of H. pylori and EBV infections in gastric cancer formation.