Helicobacter pylori and the Human Gastrointestinal Microbiota: A Multifaceted Relationship.

Helicobacter pylori is a type of Gram-negative bacteria belonging to the Proteobacteria phylum which is known to cause gastrointestinal disorders such as gastritis and gastric ulcers. Its treatment is based on current eradication regimens, which are composed of combinations of antibiotics such as clarithromycin, metronidazole, levofloxacin and amoxicillin, often combined with a proton pump inhibitor (PPI). With the development of sequencing technologies, it has been demonstrated that not only does the colonization of the gastric and gut environment by H. pylori cause microbial changes, but also the treatment regimens used for its eradication have a significant altering effect on both the gastric and gut microbiota. Here, we review current knowledge on microbiota modulations of current therapies in both environments. We also summarize future perspectives regarding H. pylori infection, the integration of probiotics into therapy and what challenges are being faced on a global basis when we talk about eradication.

Equivalence Trial of the Non-Bismuth 10-Day Concomitant and 14-Day Hybrid Therapies for Helicobacter pylori Eradication in High Clarithromycin Resistance Areas.

Background and aim: We conducted an equivalence trial of quadruple non-bismuth "concomitant" and "hybrid" regimens for H. pylori eradication in a high clarithromycin resistance area. Methods: There were 321 treatment-naïve H. pylori-positive individuals in this multicenter clinical trial randomized to either the hybrid (esomeprazole 40 mg/bid, amoxicillin 1 g/bid for 7 days, then 7 days esomeprazole 40 mg/bid, amoxicillin 1 g/bid, clarithromycin 500 mg/bid, and metronidazole 500 mg/bid) or the concomitant regimen (all medications given concurrently bid for 10 days). Eradication was tested using histology and/or a 13C-urea breath test. Results: The concomitant regimen had 161 patients (90F/71M, mean 54.5 years, 26.7% smokers, 30.4% ulcer) and the hybrid regimen had 160 (80F/80M, mean 52.8 years, 35.6% smokers, 31.2% ulcer). The regimens were equivalent, by intention to treat 85% and 81.8%, (p = 0.5), and per protocol analysis 91.8% and 87.8%, (p = 0.3), respectively. The eradication rate by resistance, between concomitant and hybrid regimens, was in susceptible strains (97% and 97%, p = 0.6), clarithromycin single-resistant strains (86% and 90%, p = 0.9), metronidazole single-resistant strains (96% and 81%, p = 0.1), and dual-resistant strains (70% and 53%, p = 0.5). The side effects were comparable, except for diarrhea being more frequent in the concomitant regimen. Conclusions: A 14-day hybrid regimen is equivalent to a 10-day concomitant regimen currently used in high clarithromycin and metronidazole resistance areas. Both regimens are well tolerated and safe.

Clinical Study on the Eradication of Helicobacter pylori by Vonoprazan Combined with Amoxicillin for 10-Day Dual Therapy.

Vonoprazan holds significant research promise for Helicobacter pylori eradication, with the goal of determining the most effective drug regimen. In this study, H. pylori patients (426) were enrolled and randomized into 3 groups: an EA14 group (20 mg of esomeprazole qid and 1000 mg of amoxicillin tid for 14 days), a VA14 group (20 mg of vonoprazan bid and 750 mg of amoxicillin qid for 14 days), and a VA10 group (20 mg of vonoprazan bid and 1000 mg of amoxicillin tid for 10 days). Key outcomes encompassed the H. pylori eradication rate, patient adverse effects, and compliance. In the EA14, VA14, and VA10 groups, H. pylori eradication rates were 89.4%, 90.1%, and 88.7% in intention-to-treat analysis, and 94.2%, 94.4%, and 94.6% in per-protocol analysis, respectively. Adverse events incidences were 14.8%, 12.7%, and 5.6%, while compliance rates were 88.7%, 90.9%, and 95.8%, respectively. Notably, the VA10 regimen demonstrated comparable H. pylori eradication rates, adverse effect incidences, and compliance levels to the EA14 and VA14 regimens.

Preoperative H. pylori Eradication Therapy Facilitates Precise Delineation in Early Gastric Cancer with Current H. pylori Infection.

INTRODUCTION: Early gastric cancer with current Helicobacter pylori infection (HpC-EGC) is common, but it is still unclear whether H. pylori eradication therapy (Hp-ET) or endoscopic submucosal dissection (ESD) should be performed first. We evaluated Hp-ETs short-term effects on horizontal boundary delineations of HpC-EGC in ESD. METHODS: Prospectively enrolled HpC-EGC patients were randomly assigned to eradication or control groups. Operation scopes of HpC-EGC lesions were delineated with marking dots at 5 mm out of the endoscopic demarcation line by an independent endoscopist, unaware of eradication status, before formal circumferential incision. As representatives, precise delineation rate, the shortest distance of all marking dots to the pathological demarcation line in all slices of one intact resected specimen (Dmin), and negative marking dot specimen rate were examined. RESULTS: Twenty-three HpC-EGC patients (25 lesions) were allocated to eradication group and 26 patients (27 lesions) were allocated to the control group with similar eradication success rates and all were differentiated type. With improving background mucosa inflammation after Hp-ET and similar gastritis-like epithelium rates, 10 lesions (40.0%) in the eradication group were of precise delineation compared to control group with 2 lesions (7.4%) (relative risk = 5.40, 95% CI 1.31-22.28). Dmin of eradication and control groups were 4.17 ± 2.52 mm and 2.67 ± 2.30 mm (p = 0.029), accompanied by 4 (14.8%) and none (0.0%) specimens that exhibited positive marking dots (p = 0.11), respectively. CONCLUSION: For HpC-EGC patients, administrating eradication medication before ESD is beneficial for the precise delineation of lesions and reducing the risk of positive horizontal resection margins.

The use of non-invasive stool tests for verification of Helicobacter pylori eradication and clarithromycin resistance.

BACKGROUND: Clarithromycin resistance of Helicobacter pylori (H. pylori) represents a major challenge in eradication therapy. In this study, we assessed if non-invasive stool tests can be used to verify successful H. pylori eradication and determine clarithromycin resistance. MATERIALS AND METHODS: In this prospective study, patients undergoing urea breath testing (UBT) for confirmation of H. pylori eradication were asked to collect the stool as both a dry fecal sample and fecal immunochemical test (FIT). Stool H. pylori antigen testing (SAT) was performed on these samples and assessed for its accuracy in eradication verification. Type and duration of antibiotic treatment were retrospectively collected from patient records and compared with clarithromycin resistance determined by PCR of stool samples. RESULTS: H. pylori eradication information was available for a total of 145 patients (42.7% male, median age: 51.2). Successful eradication was achieved in 68.1% of patients. SAT on FIT samples had similar accuracy for eradication assessment compared to dry fecal samples, 72.1% [95% CI 61.4-81.2] versus 72.2% [95% CI 60.9-81.7]. Clarithromycin resistance rate was 13.4%. CONCLUSION: H. pylori antigen testing on FIT stool samples to verify H. pylori eradication is feasible and has similar accuracy as H. pylori antigen testing on dry stool samples. Dry stool, but not FIT, was suitable for non-invasive identification of H. pylori clarithromycin resistance by rt-PCR personalizing antibiotic treatment strategies without the need for invasive diagnostics is desirable, as the cure rate of first-line empirical H. pylori treatment remains low.

Efficacy of Sequential Therapy as the First-Line Treatment in the Eradication of Helicobacter pylori.

The Helicobacter pylori infection is a significant issue in global health as it is associated with a range of gastrointestinal disorders and an elevated likelihood of developing stomach cancer. The declining efficacy of standard triple therapy (TT) as the recommended treatment can be attributed to the emergence of drug-resistant strains. Sequential therapy (ST) has been recognized as an alternative approach, wherein a combination of proton-pump inhibitor (PPI) and amoxicillin is administered for the initial five days, followed by a combination of PPI, clarithromycin, and metronidazole for the subsequent five days. In this comprehensive systematic review and meta-analysis, we have thoroughly assessed the effectiveness and tolerability of ST as a primary treatment option in comparison to TT for the eradication of H. pylori. The analysis comprised a total of 15 randomized controlled trials, encompassing a sample size of 5,219 patients. The collective findings indicate that ST exhibits promise as it achieves higher rates of eradication. Additionally, it is worth noting that this approach has the potential to yield cost savings and enhance treatment compliance when compared to TT. To summarize, this systematic review and meta-analysis provide evidence that ST is a viable option for the initial treatment of H. pylori eradication. It shows potential benefits compared to the standard TT, especially when there is resistance to clarithromycin. In order to establish ST as the preferred first-line treatment, it is imperative that additional research be conducted to address the aforementioned limitations and thoroughly investigate its long-term efficacy and safety profiles. Nevertheless, it is required that additional research be conducted in order to adequately tackle the constraints of the current studies and solidify its position as a favored treatment alternative. It is also essential to consider ST as a viable approach to improve the rates of H. pylori eradication. This method should be thoroughly examined in clinical practice to gain a deeper understanding of its effectiveness.

Triple therapy for Helicobacter pylori eradication and the risk of hypoglycemia in patients with diabetes: a population-based cohort study.

The incidence of type 2 diabetes mellitus has risen globally, from 108 million cases in 1980 to 422 million cases in 2014. Although controlling glycemic levels in patients with diabetes is crucial, insulin and sulfonylureas can cause hypoglycemic episodes and even potentially fatal events such as comas, seizures, life-threatening arrhythmias, and myocardial infarctions. Several antibiotics have been documented to cause hypoglycemic episodes; the use of antibiotics along with insulin or sulfonylureas might further increase the risk of hypoglycemia. Therefore, researchers must determine which antibiotics carry a risk of inducing severe hypoglycemic events. The prevalence of H. pylori infection remains high in most countries, and the infection is often treated with triple therapy involving amoxicillin, clarithromycin, and a proton pump inhibitor (PPI). Several case reports have reported that hypoglycemia can occur when used with patients who also take diabetes medication. Therefore, we hypothesized that patients with diabetes have an increased risk of hypoglycemic episodes when being treated with triple therapy for H. pylori infection. By analyzing medical records from Taiwan's National Health Insurance Research Database, we found a significant association between hypoglycemia and triple therapy treatment for diabetic patients with peptic ulcer disease. Prescribing triple therapy to patients with diabetes and peptic ulcers significantly increased the risk of a hypoglycemic episode (adjusted odds ratio [aOR] = 1.75, 95% confidence interval [CI]: 1.64 to 1.88, P < 0.001). Similarly, the highest aOR (5.77, 95% CI 4.82 to 6.92) was found in patients with diabetes and peptic ulcers who had hypoglycemic episodes within 30 days after triple therapy treatment. Many patients with diabetes require H.pylori eradication for peptic ulcer treatment, and vigilance toward the risk of hypoglycemia in this population is thus necessary.

Correlation analysis of endoscopic manifestations and eradication effect of Helicobacter pylori.

Background: Helicobacter pylori (H. pylori) infection is the most important risk factor for gastric cancer. Eradication of H. pylori significantly reduces the incidence and mortality of gastric cancer. H. pylori resistance to antibiotics and a gradual decline in eradication rates are gaining more and more attention. Our study aimed to address the correlation between endoscopic manifestations and the eradication effect of H. pylori. Methods: We retrospectively reviewed outpatients in our hospital with H. pylori infection undergoing eradication therapy from January 2022 to March 2023. Both the primary diagnosis and eradication of H. pylori after treatment were confirmed by a 13C urea breath test. Patients were treated with a proton pump inhibitor (PPI)-based quadruple therapy. Clinical characteristics and endoscopy manifestations within 7 days before or after patients were diagnosed with H. pylori infection were analyzed. Results: From January 2022 to March 2023, a total of 323 patients were enrolled in this study. There were 138 male patients and 185 female patients. The mean age of patients was 45.62 ± 13.04 years. The H. pylori initial eradication rate was 82.0%. Univariate analysis of factors affecting H. pylori eradication showed that sex, age, and endoscopic manifestations including diffuse redness, multiple white, and flat elevated lesions, and atrophy were significantly associated with the failure of H. pylori eradication therapy. A multivariable logistic regression model analysis of these five factors showed that patients aged over 60 years with multiple white and flat elevated lesions in the endoscopic examination are significantly less likely to eradicate H. pylori with empirical quadruple therapy. On the other hand, patients with diffuse redness were significantly more likely to eradicate H. pylori infection with empirical quadruple therapy. Conclusion: Our study shows that age over 60 years old, multiple white and flat elevated lesions in endoscopic examination are independent risk factors of initial H. pylori eradication failure with empirical quadruple therapy, while diffuse redness in endoscopic examination is a protective factor of initial H. pylori eradication failure with empirical quadruple therapy, while diffuse redness in endoscopic examination is a protective factor. For patients with these risk factors, a drug sensitivity test or H. pylori resistance gene mutation detection may be more appropriate. However, further mechanism studies or prospective studies are needed to prove our findings.

Characteristic analysis of early gastric cancer after Helicobacter pylori eradication: a multicenter retrospective propensity score-matched study.

BACKGROUND: Helicobacter pylori (H. pylori) is recognized as a type I carcinogen in gastric cancer (GC). However, GC still occurs after H. pylori eradication, and its diagnosis is more complicated. This study aimed to summarize the characteristics of early GC (EGC) after H. pylori eradication to help accurately identify EGC and avoid missed diagnosis and misdiagnosis. METHODS: A total of 81 patients of EGC after H. pylori eradication (Hp-eradicated group), resected by endoscopic submucosal dissection (ESD), and 105 cases of H. pylori infection-related EGC (control group) were assessed. After propensity-score matching, the clinical characteristics, endoscopic manifestations, and histopathological features of the 62 matched patients in each group were analyzed. We also conducted specific analyses in combination with endoscopic and histopathological images. RESULTS: There were more patients in the Hp-eradicated group who received proton pump inhibitor (PPI) for >1 year compared to the control group (p < 0.001). More patients at OLGA stages I-II before the diagnosis of EGC were in the control group (p = 0.045), especially at stage II. The mucosa in the Hp-eradicated group showed more moderate-to-severe atrophy (p = 0.047), map-like redness (p < 0.001) and mild activity (p < 0.001). The predominant histopathological types differed between the two groups (p < 0.001), and the majority of cases in the Hp-eradicated group were high-grade intraepithelial neoplasia (HGIN). Ki-67 expression was lower in the Hp-eradicated group (p = 0.025). But different eradication intervals of H. pylori have little effect on the characteristics of EGC. Furthermore, PPI uses for >1 year (p = 0.005), mucosal map-like redness (p < 0.001), moderate mucosal atrophy (p = 0.017), and mild activity of gastric mucosa (p = 0.005) were independent characteristics of EGC after H. pylori eradication. CONCLUSION: Our multicenter study revealed that EGC after H. pylori eradication was characterized by long-term PPI use, moderate mucosal atrophy, mucosal map-like redness, the mild activity of gastric mucosa, a higher proportion of HGIN cases, and lower levels of Ki-67.

EGC after H. pylori eradication was characterized by long-term PPI use, moderate mucosal atrophy, mucosal map-like redness, mild activity of gastric mucosa, a higher proportion of HGIN cases, and lower levels of Ki-67.H. pylori-positive patients at OLGA stages I-II are also more likely to progress to EGC.According to the current data, different eradication intervals of H. pylori have little effect on the characteristics of EGC.

Analysis of risk factors for ulcer recurrence and upper gastrointestinal bleeding in children with peptic ulcer treated with Helicobacter pylori eradication therapy.

Background: The incidence of peptic ulcer disease (PUD) has been increasing yearly, especially in the adolescent population. The eradication of Helicobacter pylori (H. pylori) may reduce recurrence and bleeding to some extent, but it does not completely change the clinical status of PUD. Therefore, this study aims to analyze the risk factors for ulcer recurrence and upper gastrointestinal bleeding after H. pylori eradication therapy in order to provide a reference for reducing the risk of PUD and improving the quality of life of patients. Methods: We retrospectively analyzed 536 adolescent patients who developed peptic ulcer and received H. pylori eradication therapy from June 2016 to July 2021. The relationship between the clinical characteristics of the patients and gastrointestinal bleeding and recurrence was analyzed using the t-test and chi-squared test. Binary logistic regression was used to analyze the independent risk factors for the occurrence of bleeding and recurrence. Results: A total of 536 patients were included in this retrospective study. Gender, history of ulcers, number, size, location and staging of ulcers, and application of nonsteroidal anti-inflammatory drugs (NSAIDs), and other characteristics were significantly different between the bleeding and nonbleeding groups (P<0.05); family history of upper gastrointestinal ulcer, history of ulcers, number and size of ulcers and application of NSAIDs, and other characteristics were significantly different between the recurrent and nonrecurrent groups (P<0.05). Binary logistic regression analysis showed that history of ulcers, number and location of ulcers, coagulation abnormalities, and other characteristics were independent risk factors for the occurrence of bleeding; the occurrence of previous bleeding, number and size of ulcers, and other characteristics were independent risk factors for recurrence. Conclusions: In the clinical treatment of adolescent patients, it is important to pay high attention to clinical characteristics, such as the patient's previous ulcer history, the size, number and location of ulcers, and coagulation function, so as to adopt individualized treatment methods to effectively reduce the harmfulness of the disease in response to the risk factors of ulcer bleeding and recurrence after H. pylori eradication therapy. This can decrease the occurrence of complications and improve the prognosis of patients.

An increasing trend of gastric cancer deaths and inadequate preventive measures in elderly adults.

BACKGROUND: Japan became the world's first country to cover Helicobacter pylori eradication for chronic gastritis under its National Health Insurance (NHI) system in February 2013. Thereafter, H. pylori eradication dramatically increased and gastric cancer deaths began to decrease in Japan. However, the details of gastric cancer deaths and its prevention in the very elderly have not been fully elucidated. METHODS: We analyzed the temporal trend of gastric cancer deaths referencing data from Ministry of Health, Labour and Welfare reports and "Cancer Statistics in Japan-2021" and assessed the numbers of H. pylori test and gastric cancer screening using a national database and a report of cancer screening in Shimane Prefecture, respectively. RESULTS: Although gastric cancer deaths in total population have clearly decreased since 2013, those in people aged 80 years and older are still increasing. People aged 80 years and older represent 9% of the total population and accounted for half of all gastric cancer deaths in 2020. The numbers of H. pylori eradication and gastric cancer screening in people aged 80 years and older were 25% and 25% of those in other generations, respectively. CONCLUSION: In spite of a dramatic increase in H. pylori eradication and a clear decrease in gastric cancer deaths in Japan, gastric cancer deaths in people aged 80 years and older are increasing. This might be due to fewer H. pylori eradication in the elderly than in other generations, indicating the difficulty of gastric cancer prevention in the very elderly.

Gastric microbiota dysbiosis and Helicobacter pylori infection.

Helicobacter pylori (H. pylori) infection is one of the most common causes of gastric disease. The persistent increase in antibiotic resistance worldwide has made H. pylori eradication challenging for clinicians. The stomach is unsterile and characterized by a unique niche. Communication among microorganisms in the stomach results in diverse microbial fitness, population dynamics, and functional capacities, which may be positive, negative, or neutral. Here, we review gastric microecology, its imbalance, and gastric diseases. Moreover, we summarize the relationship between H. pylori and gastric microecology, including non-H. pylori bacteria, fungi, and viruses and the possibility of facilitating H. pylori eradication by gastric microecology modulation, including probiotics, prebiotics, postbiotics, synbiotics, and microbiota transplantation.

Success rate of helicobacter pylori eradication using vonoprazan-based triple therapy as first-line treatment at a tertiary hospital in Baguio City

Background@#Helicobacter pylori is acknowledged to cause chronic gastritis and peptic ulcer disease and is also implicated in gastric carcinoma and B cell mucosa-associated lymphoid tissue (MALT) lymphoma development. It has infected at least half of the world’s population. Proton Pump Inhibitors (PPIs) have been the conventional antacid of choice for H. pylori eradication triple therapy, while vonoprazan is a novel drug of its class that was recently studied but is limited to an oral form which makes it less feasible in cases of acute gastrointestinal bleeding. According to several systematic reviews and meta-analyses, the vonoprazan-based triple therapy regimen for H. pylori eradication is a non-inferior treatment to traditional PPI-based treatment when given in 1 week for patients having no active gastrointestinal bleeding. Likewise, a safety profile has been established with its use, offering an alternative treatment option.@*Objectives@#The research aims to identify the H. pylori eradication rate among H. pylori-positive patients who received a vonoprazan-based triple therapy regimen as outpatients, describe their clinicodemographic profile, and identify potential side effects associated with the treatment.@*Methods@#This study utilized a cross-sectional study design in a single tertiary institution from January 2018 to December 2020. Descriptive and inferential statistics were used in data analysis. Frequency and percentage were utilized to determine the success and failure rates of H. pylori eradication, describe the clinicodemographic profile of patients who underwent vonoprazan-based triple therapy, and the potential side effects with treatment. The chi-square test of independence was applied to assess the significant difference in the successful and failed eradication rates across the clinicodemographic profile. A P-value of <0.05 was considered statistically significant, and statistical analyses were conducted using SPSS version 20.0.@*Results@#32 (91%) had successful H. pylori eradication, with the majority of them determined by a negative 13C-UBT result (62.8%) and the rest with a negative H. pylori stool antigen test (28.6%). The majority of patients undergoing H. pylori eradication using a vonoprazan-based regimen with documented successful eradication belonged to the 19 to 39 years old group (50%), clerical support workers (40.63%), with a chief complaint of abdominal pain (46.88%), with no known co- morbid illness (75%), and with endoscopic finding limited to antral gastritis alone (46.88%). This study described only two documented side effects of treatment: diarrhea and abdominal pain (2.9%).@*Conclusion@#Vonoprazan-based triple therapy, given at 20 mg twice daily for 7 days, has shown a high H. pylori eradication rate among hemodynamically stable patients, without active bleeding, and treated on an outpatient basis. There was a significant difference in eradication success and failure across co-morbidities, with a higher success rate in those without co-morbid illness. A high success rate was also seen in patients <40 years of age, with a single chief complaint, and with antral gastritis as the sole endoscopic finding.

Refractory Helicobacter pylori infection and the gastric microbiota.

Background: Curing refractory Helicobacter pylori infection is difficult. In addition, there is currently no research on the gastric microbiota of refractory H. pylori infection. Methods: We designed a clinical retrospective study involving 32 subjects divided into three groups: 1. nAGHp.a, treatment-naïve patients with H. pylori infection; 2. nAGHp.b, H. pylori-negative patients; and 3. EFHp.a, patients with refractory H. pylori infection. Gastric mucosal samples from the biobank of our research center were collected for 16S rRNA sequencing analysis and bacterial functions were predicted via PICRUSt. Results: There were significant differences between the H. pylori- positive group and the H. pylori-negative group in species diversity, gastric microbiota structure, and bacterial function. The beneficial Lactobacillus in the H. pylori-positive group were significantly enriched compared with those in the refractory H. pylori infection group. The bacterial interaction network diagram suggested that the microbiota interactions in the refractory H. pylori infection group decreased. The gastric microbiota of the refractory H. pylori infection group was enriched in the pathways of metabolism and infectious diseases (energy metabolism, bacterial secretion system, glutathione metabolism, protein folding and associated processing, sulphur metabolism, membrane and intracellular structural molecules, lipopolysaccharide biosynthesis, ubiquinone and other terpenoid-quinone biosynthesis, inorganic ion transport and metabolism, and metabolism of cofactors and vitamins) when compared with the H. pylori-positive group without treatment based on PICRUSt analysis. Conclusion: Significant alterations occurred in the gastric microbiota when eradication of H. pylori failed multiple times. A history of eradication of multiple H. pylori infections leads to an imbalance in the gastric mucosal microbiota to a certain extent, which was mainly reflected in the inhibition of the growth of beneficial Lactobacillus in the stomach. Patients with refractory H. pylori infection may be at a higher risk of developing gastric cancer than other H. pylori-positive patients.

Evidence-based clinical practice guidelines for functional dyspepsia 2021.

BACKGROUND: Functional dyspepsia (FD) is a disorder that presents with chronic dyspepsia, which is not only very common but also highly affects quality of life of the patients. In Japan, FD became a disease name for national insurance in 2013, and has been gradually recognized, though still not satisfactory. Following the revision policy of Japanese Society of Gastroenterology (JSGE), the first version of FD guideline was revised this time. METHOD: Like previously, the guideline was created by the GRADE (grading of recommendations assessment, development and evaluation) system, but this time, the questions were classified to background questions (BQs, 24 already clarified issues), future research questions (FRQs, 9 issues cannot be addressed with insufficient evidence), and 7 clinical questions that are mainly associated with treatment. RESULTS AND CONCLUSION: These revised guidelines have two major features. The first is the new position of endoscopy in the flow of FD diagnosis. While endoscopy was required to all cases for diagnosis of FD, the revised guidelines specify the necessity of endoscopy only in cases where organic disease is suspected. The second feature is that the drug treatment options have been changed to reflect the latest evidence. The first-line treatment includes gastric acid-secretion inhibitors, acetylcholinesterase (AChE) inhibitors (acotiamide, a prokinetic agent), and Japanese herbal medicine (rikkunshito). The second-line treatment includes anxiolytics /antidepressant, prokinetics other than acotiamide (dopamine receptor antagonists, 5-HT4 receptor agonists), and Japanese herbal medicines other than rikkunshito. The patients not responding to these treatment regimens are regarded as refractory FD.

Helicobacter pylori induced Immune Thrombocytopenic Purpura and perspective role of Helicobacter pylori eradication therapy for treating Immune Thrombocytopenic Purpura.

Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterised by production of autoantibodies against platelet surface antigens. Recent studies have demonstrated a paramount association of ITP and Helicobacter pylori (H-pylori) infection with significant rise in platelet count following H-pylori eradication therapy. The H-pylori infection induced ITP is validated by many proposed mechanisms such as molecular mimicry due to production of autoantibodies against H-pylori surface virulent factors (CagA) and cross reactivity of these antibodies with platelet surface antigens (GP IIb/IIIa, GP Ib/IX, and GP Ia/IIa), phagocytic perturbation due to enhanced phagocytic activity of monocytes, enhanced dendritic cell numbers and response, platelets aggregation due to presence of anti- H-pylori IgG and von Willebrand factor (vWf) and finally host immune response against H-pylori virulent factors CagA and VacA leading to ITP. The effectiveness of H-pylori eradication therapy has also been demonstrated with platelet count being used as a predictive factor for assessment of treatment efficacy. Out of 201 patients 118 were responding to the triple therapy and remaining 83 patients were non-responders, showing the response rate of 58.7%. Out of 118 responders 69 patients were showing complete response (CR) and 49 were showing partial response (PR) to the H-pylori eradication therapy. However, more studies are required to elucidate this association and treatment efficacy.

Role of Helicobacter pylori eradication in patients with functional dyspepsia.

BACKGROUND: Helicobacter pylori (H. pylori) is implicated in the pathogenesis of functional dyspepsia (FD). There is conflicting data regarding the benefit of H. pylori eradication for symptom relief in FD. AIMS: To study the benefit of eradicating H. pylori in patients with FD as compared to standard medical treatment (SMT). Secondary aims were to find efficacy of H. pylori eradication therapy, recurrence of H. pylori after eradication, and predictors of efficacy. METHODS: Consecutive adult patients of FD (ROME IV) with H. pylori infection presenting in the outpatient department of our hospital were enrolled. Patients with Global Overall Symptom (GOS) scale > 2 and H. pylori infection were included. Patients were randomized into two groups: group 1 received H. pylori eradication therapy and group 2 received SMT. Treatment success was defined as symptom relief (GOS score < 2 and reduction by at least 2 points at 6 months) and H. pylori eradication was defined as stool antigen negative at 4 weeks. RESULTS: Of 329 participants with FD, 253 were H. pylori positive (rapid urease test and stool antigen test) (76.89%). After exclusions, 202 were randomized into two groups of 101 each. Thirty-two patients in group 1 and 31 in group 2 had treatment success (31.7% vs. 30.7%, p=1.000). The efficacy of H. pylori eradication therapy was 74.46% (70/94). H. pylori reinfection rate was 26.02% (19/73). CONCLUSIONS: H. pylori eradication therapy does not provide additional benefit in symptom relief in patients with FD as compared with SMT. TRIAL REGISTRATION: NCT04697641 (retrospectively registered on www.clinicaltrials.gov in January 2021).

The impact of Helicobacter pylori infection, eradication therapy, and probiotics intervention on gastric microbiota in young adults.

BACKGROUND: The impact of probiotics on non-Helicobacter pylori gastric microbiota and its role in microbial restoration after eradication were relatively unknown. We aimed to explore the effect of H. pylori eradication and probiotic intervention on gastric microbiota in young adults. METHODS: Fifty-six H. pylori-negative and 95 H. pylori-positive subjects aged 19-30 were included in this study. H. pylori-infected individuals were randomly assigned to quadruple therapy, probiotics supplemented quadruple therapy, or probiotics monotherapy group. Gastric mucosa and gastric juice samples were collected before and 2 months after treatment for 16SrRNA gene sequencing. RESULTS: The gastric microbial community structure and composition differed from H. pylori-negative subjects 2 months after successful H. pylori eradication. The α diversity of gastric mucosal microbiota significantly increased and was higher than H. pylori-negative subjects, while the α diversity of gastric juice microbiota decreased and was lower than the H. pylori-negative. After probiotics supplemented eradication treatment, Bifidobacterium was enriched in gastric mucosa, Lactobacillus was enriched in gastric juice, potentially pathogenic bacteria such as Fusobacterium and Campylobacter decreased, and the microbial diversity was closer to that of H. pylori-negative subjects compared to quadruple therapy group. Probiotics monotherapy significantly altered the diversity, community structure, and composition of gastric microbiota but showed no advantage in H. pylori inhibition and upregulating beneficial bacteria such as Bifidobacterium and Lactobacillus and related metabolism pathways. Certain potentially pathogenic bacteria such as Fusobacterium increased after probiotic monotherapy. CONCLUSION: H. pylori eradication significantly disrupted gastric microbiota in young adults and could not be restored in a short time. Probiotics supplementation partially helped restore the gastric dysbiosis caused by eradication therapy, but it might be unnecessary for H. pylori-infected young adults to take probiotics alone.

Dietary multivalent anti-Helicobacter pylori immunoglobulin Y significantly increase the H. pylori eradication and improve the clinical symptoms in patients.

BACKGROUND: The oral chicken immunoglobulin Y (IgY) as a novel model of immunotherapy to control Helicobacter pylori (H. pylori, Hp) infection has gained much interest in recent years. However, none of the current IgY therapies showed a total eradication of H. pylori on patients. METHODS: In this report, the recombinant antigens of H. pylori, including UreB (1710 bp), BabA2 (1269 bp), and FlaA (399 bp), were, respectively, expressed and purified, and then mixed and subjected to immunize laying hens for the preparation of multivalent anti-H. pylori immunoglobulin Y (anti-Hp mIgY). Next, the biological activities of anti-Hp mIgY, including the recognition to antigens and the inhibition on H. pylori growth, were tested. Moreover, to perform a clinical trial, 94 Hp-infected patients, according to the values of 13 C urea breath test and the characteristics of gastroscopy of volunteers, were enrolled to evaluate the effects of dietary anti-Hp mIgY against H. pylori infection. After continuous dietary of anti-Hp mIgY for 2 weeks, the oral administration was terminated. The clinical symptoms of the patients were followed up at 2nd, 4th, and 6th week, respectively, and the 13 C urea breath test were re-examined at 6th week. RESULTS: The anti-Hp mIgY could bind to recombinant antigens very well, and the titers of anti-Hp mIgY to UreB, Baba2, and FlaA, are 62.5, 125, and 250 µg/ml, respectively. The in vitro antibacterial test showed that the 2 mg/ml of anti-Hp mIgY could completely inhibit the H. pylori growth for 36 h. After a 2-week dietary of anti-Hp mIgY, the value of 13 C urea breath test was significantly decreased by 56.0% (25.9 ± 14.1 vs 11.4 ± 9.78, p < 0.001), the total improvement rate of clinical symptoms in volunteers was 87.3%, and the H. pylori eradication rate was 30.6%. CONCLUSION: Two-week dietary of anti-Hp mIgY greatly improved the clinical symptoms and the quality of life of Hp-infected patients, and the H. pylori eradication rate reached up to 30.6%.

Recent progress in gastric cancer prevention.

Gastric cancer remains a major challenge to public health on a global scale, causing the loss of 19 million disability-adjusted life years worldwide in 2017. The future burden will increase due to population growth and ageing. Considering its absolute burden and persisting disparities, in addition to the substantial prevalence of Helicobacter pylori infection worldwide that is treatable, gastric cancer is a logical target for urgent global action for prevention. In this review, we discuss recent progress in gastric cancer prevention and propose a concerted international effort to implement population-based H. pylori treatment programmes, as the best evidence-based strategy that is currently available for gastric cancer prevention, in the context of demonstration projects in selected populations, to be later scaled up. It is time for urgent action to reduce the important loss of life and productivity caused by this preventable malignancy.