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.     

Ins and outs of Helicobacter pylori association with autoimmune rheumatic diseases

Helicobacter pylori (H. pylori) infection is widely prevalent throughout worldwide. H. pylori manage a long-term survival in hostile environment of human stomach leading to peptic ulcer diseases and gastric cancer. But mostly infected person remains asymptomatic. Its chronic interaction with immune system makes H. pylori as an attractive candidate for the researchers to study its association with autoimmune diseases. This article presents a review of the literature on the association of H. pylori infection in selective autoimmune rheumatic diseases (RD). The authors used MeSH terms “Helicobacter pylori” with “rheumatoid arthritis,”“systemic lupus erythematosus,” or “fibromyalgia” to search PubMed database. All relevant studies identified were included. Despite extensive medical advancement many questions on role of H. pylori infection in autoimmune RD still remain unanswered. Further studies are therefore needed to address the role of H. pylori in pathogenesis of RD.     

Structural modifications of Helicobacter pylori lipopolysaccharide:An idea for how to live in peace

In this review,we discuss the findings and concepts underlying the"persistence mechanisms"of Helicobacter pylori(H.pylori),a spiral-shaped,Gram-negative rod bacterium that was discovered as a gastric pathogen by Marshall and Warren in 1984.H.pylori colonizes the gastric mucosa of nearly half of the human population.Infections appear in early childhood and,if not treated,persist for life.The presence or absence of symptoms and their severity depend on multiple bacterial components,host susceptibility and environmental factors,which allow H.pylori to switch between pathogenicity and commensalism.Many studies have shown that H.pylori components may facilitate the colonization process and the immune response of the host during the course of H.pylori infection.These H.pylori-driven interactions might result from positive or negative modulation.Among the negative immunomodulators,a prominent position is occupied by a vacuolating toxin A(VacA)and cytotoxin-associated gene A(CagA)protein.However,in light of the recent studies that are presented in this review,it is necessary to enrich this panel with H.pylori lipopolysaccharide(LPS).Together with CagA and VacA,LPS suppresses the elimination of H.pylori bacteria from the gastric mucosa by interfering with the activity of innate and adaptive immune cells,diminishing the inflammatory response,and affecting the adaptive T lymphocyte response,thus facilitating the development of chronic infections.The complex strategy of H.pylori bacteria for survival in the gastric mucosa of the host involves both structural modifications of LPS lipid A to diminish its endotoxic properties and the expression and variation of Lewis determinants,arranged in O-specific chains of H.pylori LPS.By mimicking host components,this phenomenon leaves these bacteria"invisible"to immune cells.Together,these mechanisms allow H.pylori to survive and live for many years within their hosts.     

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.     

Helicobacter pylori infection: Beyond gastric manifestations

Helicobacter pylori(H. pylori) is a bacterium that infects more than a half of world's population. Although it is mainly related to the development of gastroduodenal diseases, several studies have shown that such infection may also influence the development and severity of various extragastric diseases. According to the current evidence, whereas this bacterium is a risk factor for some of these manifestations, it might play a protective role in other pathological conditions. In that context, when considered the gastrointestinal tract, H. pylori positivity have been related to Inflammatory Bowel Disease, Gastroesophageal Reflux Disease, Non-Alcoholic Fatty Liver Disease, Hepatic Carcinoma, Cholelithiasis, and Cholecystitis. Moreover, lower serum levels of iron and vitamin B12 have been found in patients with H. pylori infection, leading to the emergence of anemias in a portion of them. With regards to neurological manifestations, a growing number of studies have associated that bacterium with multiple sclerosis, Alzheimer's disease, Parkinson's disease, and Guillain-Barré syndrome. Interestingly, the risk of developing cardiovascular disorders, such as atherosclerosis, is also influenced by the infection. Besides that, the H. pylori-associated inflammation may also lead to increased insulin resistance, leading to a higher risk of diabetes mellitus among infected individuals. Finally, the occurrence of dermatological and ophthalmic disorders have also been related to that microorganism. In this sense, this minireview aims to gather the main studies associating H. pylori infection with extragastric conditions, and also to explore the main mechanisms that mayexplain the role of H. pylori in those diseases.     

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.     

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.     

Intersections between innate immune response and gastric cancer development

Worldwide, gastric cancer(GC) is the fifth most commonly diagnosed malignancy. It has a reduced prevalence but has maintained its poor prognosis being the fourth leading cause of deaths related to cancer. The highest mortality rates occur in Asian and Latin American countries, where cases are usually diagnosed at advanced stages. Overall, GC is viewed as the consequence of a multifactorial process, involving the virulence of the Helicobacter pylori(H. pylori) strains, as well as some environment...     

Chinese Helicobacter pylori vaccine: Solution for an old challenge?

Helicobacter pylori(H. pylori) is an important cause for gastric cancer in high risk individuals. H. pylori colonizes more than 50% of the world's population and associated peptic ulcer disease and gastric malignancy have important public health implications. It has been classified as a class Ⅰ carcinogen in 1994 by the World Health Organization. Clinicians are often prompted to eliminate the infection the moment it is detected. This also, unfortunately, led to reckless use of antibiotics and reports of increasing resistance are now worldwide. Each year, many of people die from gastric cancer; thus application of effective vaccine can reduce this relatively high mortality worldwide. H. pylori can be eliminated by antibiotics but efficacy is sharply decreasing. Moreover, current therapy is also expensive and with side effects. Vaccine may be the best solution to the above problem but there are many challenges in producing such an effective therapeutic vaccine. Recently, the Chinese group published in Lancet, a single-center, randomized, phase Ⅲ study of an oral recombinant vaccine(Urease B subunit fused with heat-labile enterotoxin B derived from Escherichia coli) prescribed in the Chinese children(6-15 years) without a history of H. pylori infection. This review provides an insight into this new solution for an old challenge.     

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.     

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.     

Increased expression of tyrosine phosphatase SHP-2 in Helicobacter pylori-infected gastric cancer

AIM:To explore the alteration of tyrosine phosphatase SHP-2 protein expression in gastric cancer and to assess its prognostic values.METHODS:Three hundred and five consecutive cases of gastric cancer were enrolled into this study.SHP-2 expression was carried out in 305 gastric cancer specimens,of which 83 were paired adjacent normal gastric mucus samples,using a tissue microarray immunohistochemical method.Correlations were analyzed between expression levels of SHP-2 protein and tumor parameters or clinical outcomes.Serum anti-Helicobacter pylori(H.pylori) immunoglobulin G was detected with enzyme-linked immunosorbent assay.Cox proportional hazards model was used to evaluate prognostic values by compassion of the expression levels of SHP-2 and disease-specific survivals in patients.RESULTS:SHP-2 staining was found diffuse mainly in the cytoplasm and the weak staining was also observed in the nucleus in gastric mucosa cells.Thirty-two point five percent of normal epithelial specimen and 62.6% of gastric cancer specimen were identified to stain with SHP-2 antibody positively(P < 0.001).Though SHP-2 staining intensities were stronger in the H.pylori(+) group than in the H.pylori(-) group,no statistically significant difference was found in the expression levels of SHP-2 between H.pylori(+) and H.pylori(-) gastric cancer(P = 0.40).The SHP-2 expression in gastric cancer was not significantly associated with cancer stages,lymph node metastases,and distant metastasis of the tumors(P = 0.34,P = 0.17,P = 0.52).Multivariate analysis demonstrated no correlation between SHP-2 expression and disease-free survival(P = 0.86).CONCLUSION:Increased expression of SHP-2 protein in gastric cancer specimen suggesting the aberrant upregulation of SHP-2 protein might play an important role in the gastric carcinogenesis.     

Olfactomedin-4 in digestive diseases: A mini-review

Olfactomedin-4(OLFM4, GW112, h GC-1) is a glycoprotein belonging to the olfactomedin family. The expression of OLFM4 is strong in the small intestine, colon and prostate, and moderate in the stomach and bone marrow. Previous studies have revealed that OLFM4 is closely associated with many digestive diseases. Up-regulation of OLFM4 has been detected in the Helicobacter pylori(H. pylori)-infected gastric mucosa, inflammatory bowel disease tissue and gastrointestinal malignancies, including gastric cancer, colorectal cancer, pancreatic cancer and gallbladder cancer. Downregulation of OLFM4 has also been detected in some cases, such as in poorly differentiated, advancedstage and metastatic tumors. Studies using OLFM4-deficient mouse models have revealed that OLFM4 acts as a negative regulator of H. pylori-specific immune responses and plays an important role in mucosal defense in inflammatory bowel disease. Patients with OLFM4-positive gastric cancer or colorectal cancer have a better survival rate than OLFM4-negative patients. However, the prognosis is worse in pancreatic cancer patients with high levels of expression of OLFM4. The NF-κB, Notch and Wnt signaling pathways are involved in the regulation of OLFM4 expression in digestive diseases, and its role in pathogenesis is associated with anti-inflammation, apoptosis, cell adhesion and proliferation. OLFM4 may serve as a potential specific diagnostic marker and a therapeutic target in digestive diseases. Further studies are required to explore the clinical value of OLFM4.     

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.     

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.     

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.     

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.     

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.