Role of Helicobacter pylori virulence factors and alteration of the Tumor Immune Microenvironment: challenges and opportunities for Cancer Immunotherapy.

Various forms of malignancies have been linked to Helicobacter pylori. Despite advancements in chemotherapeutic and surgical approaches, the management of cancer, particularly at advanced stages, increasingly relies on the integration of immunotherapy. As a novel, safe therapeutic modality, immunotherapy harnesses the immune system of the patient to treat cancer, thereby broadening treatment options. However, there is evidence that H. pylori infection may influence the effectiveness of immunotherapy in various types of cancer. This association is related to H. pylori virulence factors and the tumor microenvironment. This review discusses the influence of H. pylori infection on immunotherapy in non-gastrointestinal and gastrointestinal tumors, the mechanisms underlying this relationship, and directions for the development of improved immunotherapy strategies.

Oral administration of bacterial probiotics improves Helicobacter pylori-induced memory impairment in rats: Insights from behavioral and biochemical investigations.

There are numerous evidence supporting the association between Helicobacter pylori (H. pylori) infection and the occurrence of cognitive deficits in humans. In this regard, treatment of H. pylori infection has been suggested as an effective strategy to decelerate the neurodegenerative processes of memory deficits in AD patients. Numerous studies support the beneficial effects of probiotics on various pathological conditions, particularly cognitive deficits, however, this concern has not been addressed in relation to the memory impairment induced by H. pylori infection. In the present study, we aimed to reveal whether oral administration of two bacterial probiotics (including Lactobacillus rhamnosus and Lactobacillus plantarum), could ameliorate H. pylori-induced memory deficits at behavioral level in rats. Besides, cellular mechanisms were investigated by biochemical methods to find out how probiotic effects are mediated in hippocampal circuitry. Male Wistar rats were infected by H. pylori for 3 consecutive days, then probiotic treatment was done for the next 3 days and after a drug-free period (12 days), animals were assessed by Morris Water Maze and Novel Object Recognition tests. Finally, rats were euthanized by CO2 and hippocampal tissues were excised for biochemical measurements. Results indicated that H. pylori infection markedly impairs memory function in rats which is associated with alterations of oxidative, inflammatory, neurotrophic, and cholinergic markers. Interestingly, treatment with either of the probiotics alone or in combination, significantly improved the H. pylori-induced memory deficits and this was associated with restoration of balance in biochemical factors within the hippocampal neurons.

[1983-2023 - Four decades Helicobacter pylori - what's next?] / 1983­2023 ­ Vierzig Jahre Helicobacter pylori ­ und nun?

Four decades ago the discovery of Helicobacter pylori was first reported in the international medical literature. Since then, there have been significant developments in basic and clinical science that have been translated into daily clinical practice. Changes in the management of H. pylori infection have occurred in diagnostic algorithms, indications for therapy and therapy itself. A special focus is directed to strategies of gastric cancer prevention.This manuscript briefly reviews the milestone in 40 years of H. pylori management.

The modulatory effect of Lactobacillus gasseri ATCC 33323 on autophagy induced by extracellular vesicles of Helicobacter pylori in gastric epithelial cells in vitro.

Helicobacter pylori has been recognized as a true pathogen, which is associated with various gastroduodenal diseases, and gastric adenocarcinoma. The crosstalk between H. pylori virulence factors and host autophagy remains challenging. H. pylori can produce extracellular vesicles (EVs) that contribute to gastric inflammation and malignancy. Some probiotic strains have been documented to modulate cell autophagy process. This study was aimed to investigate the modulatory effect of cell-free supernatant (CFS) obtained from Lactobacillus gasseri ATCC 33323 on autophagy induced by H. pylori-derived EVs. EVs were isolated from two clinical H. pylori strains (BY-1 and OC824), and characterized using transmission electron microscopy (TEM) and dynamic light scattering (DLS). The viability of AGS cells was assessed after exposure to different concentrations of H. pylori EVs, and L. gasseri CFS. Based on MTT assay and Annexin V-FITC/PI staining, 50 µg/ml of H. pylori EVs and 10 % v/v of L. gasseri CFS were used for further cell treatment experiments. Autophagy was examined using acridin orange (AO) staining, RT-qPCR analysis for autophagy mediators (LC3B, ATG5, ATG12, ATG16L1, BECN1, MTOR, and NOD1), and western blotting for LC3B expression. H. pylori EVs were detected to range in size from 50 to 200 nm. EVs of both H. pylori strains and L. gasseri CFS showed no significant effect on cell viability as compared to untreated cells. H. pylori EVs promoted the development of acidic vesicular organelles and the expression of autophagy-related genes (LC3B, ATG5, ATG12, ATG16L1, BECN1, and NOD1), and decreased the expression of MTOR in AGS cells at 12 and 24 h time periods. In addition, the production of LC3B was increased following 12 h of treatment in AGS cells. In contrast, L. gasseri CFS effectively inhibited EVs-induced autophagy, as evidenced by reduced acidic vesicular organelle formation and modulation of autophagy markers. Our study indicated that L. gasseri CFS can effectively suppress H. pylori EV-induced autophagy in AGS cells. Further investigations are required to decipher the mechanism of action L. gasseri CFS and its metabolites on autophagy inhibition induced by H. pylori.

Lactobacillus reuteri in digestive system diseases: focus on clinical trials and mechanisms.

Objectives: Digestive system diseases have evolved into a growing global burden without sufficient therapeutic measures. Lactobacillus reuteri (L. reuteri) is considered as a new potential economical therapy for its probiotic effects in the gastrointestinal system. We have provided an overview of the researches supporting various L. reuteri strains' application in treating common digestive system diseases, including infantile colic, diarrhea, constipation, functional abdominal pain, Helicobacter pylori infection, inflammatory bowel disease, diverticulitis, colorectal cancer and liver diseases. Methods: The summarized literature in this review was derived from databases including PubMed, Web of Science, and Google Scholar. Results: The therapeutic effects of L. reuteri in digestive system diseases may depend on various direct and indirect mechanisms, including metabolite production as well as modulation of the intestinal microbiome, preservation of the gut barrier function, and regulation of the host immune system. These actions are largely strain-specific and depend on the activation or inhibition of various certain signal pathways. It is well evidenced that L. reuteri can be effective both as a prophylactic measure and as a preferred therapy for infantile colic, and it can also be recommended as an adjuvant strategy to diarrhea, constipation, Helicobacter pylori infection in therapeutic settings. While preclinical studies have shown the probiotic potential of L. reuteri in the management of functional abdominal pain, inflammatory bowel disease, diverticulitis, colorectal cancer and liver diseases, its application in these disease settings still needs further study. Conclusion: This review focuses on the probiotic effects of L. reuteri on gut homeostasis via certain signaling pathways, and emphasizes the importance of these probiotics as a prospective treatment against several digestive system diseases.

Inhibitory activity of Limosilactobacillus reuteri isolated from camel milk against Helicobacter pylori effects in human gastric epithelial cells.

This study aimed to evaluate anti-Helicobacter pylori effects of Limosilactobacillus reuteri 2892 (L. reuteri 2892) isolated from camel milk in GC cell lines (AGS and MKN). From 15 camel milk samples, 132 microbial strains were isolated. Based on microbial and biochemical analysis, 11 potential probiotic candidates were selected. The potential probiotic candidates were assayed for anti-H. pylori activity, and the strain with the highest anti-H. pylori activity was identified genotypically. Based on 16S rDNA sequencing, the selected strain with the best activity against H. pylori (inhibition zone = 15.5 ± 0.8) belonged to the Lactobacillus reuteri strain 2892. Cell treatment with H. pylori HC-113 inhibits gene expression of Claudin-4, ZO-1, MUC5AC, and MUC2 in gastric cells, which are attenuated by L. reuteri 2892. The simulative effects of H. pylori HC-113 on the cell migration and invasion of gastric cells were lost when cells were cotreated with L. reuteri 2892. Cell treatment with H. pylori HC-113 promoted cell death, whereas cotreatment with L. reuteri 2892 markedly decreased necrotic and late apoptotic cells. The present study demonstrates that L. reuteri 2892 has potent anti-H. pylori effects and thus can be considered as an alternative protective agent against inflammatory effects of H. pylori in gastric cells.

Does enteral nutrition through a percutaneous endoscopic gastrostomy, attenuate Helicobacter pylori colonization?: is it worth mentioning?

OBJECTIVE: In patients who experience difficulties in oral feeding, alimentary intake can be supported by creating direct access into the stomach through a percutaneous endoscopic gastrostomy. The present study purposed to compare naïve and exchanged percutaneous endoscopic gastrostomy tubes in terms of Helicobacter pylori infection and other clinical characteristics. METHODS: A total of 96 cases who underwent naïve or exchanged percutaneous endoscopic gastrostomy procedures with various indications were incorporated into the study. The patients' demographic data, such as age and gender, etiology of percutaneous endoscopic gastrostomy, anti-HBs status, Helicobacter pylori status, the presence of atrophy and intestinal metaplasia, biochemical parameters, and lipid profiles, had been analyzed. In addition, the anti-HCV and anti-HIV statuses had also been evaluated. RESULTS: The most common indication for percutaneous endoscopic gastrostomy placement was dementia in 26 (27.08%) cases (p=0.033). The presence of Helicobacter pylori positivity was significantly lower in the exchange group compared to the naïve group (p=0.022). Total protein, albumin, and lymphocyte levels were significantly higher in the exchange group compared to the naïve group (both p=0.001), and the mean calcium, hemoglobin, and hematocrit levels were statistically significantly higher in the exchange group (p<0.001). CONCLUSION: Preliminary outcomes of the present study revealed that enteral nutrition attenuates the incidence of Helicobacter pylori infection. Considering the acute-phase reactant, the significantly lower ferritin values in the exchange group suggest that there is no active inflammatory process in the patients and that immunity is sufficient.

Is Helicobacter pylori Anyway Pathogen in Children?

Helicobacter pylori (H. pylori) infection is a continuous challenge for both gastroenterologists and pediatricians. The international guidelines regarding diagnostic and treatment pathways differ between adults and children. The pediatric guidelines are more restrictive because children are rarely affected by serious consequences, particularly in Western countries. Therefore, infected children should be treated only after a careful case-by-case evaluation by a pediatric gastroenterologist. In any case, recent studies are confirming an increasingly all-around pathological role of H. pylori even in asymptomatic children. For these reasons, following the current evidence, we feel that H. pylori-infected children could be treated starting in pre-adolescence, particularly in Eastern countries, because their stomachs have already begun to develop the biomarkers of gastric damage. Therefore, we believe that H. pylori is anyway pathogen in children. Nevertheless, the possible beneficial role of H. pylori in humans has not yet been conclusively disproved.

The status quo of short videos as a health information source of Helicobacter pylori: a cross-sectional study.

Background: Health education about Helicobacter pylori (H. pylori) is one of the most effective methods to prevent H. pylori infection and standardize H. pylori eradication treatment. Short videos enable people to absorb and remember information more easily and are an important source of health education. This study aimed to assess the information quality of H. pylori-related videos on Chinese short video-sharing platforms. Methods: A total of 242 H. pylori-related videos from three Chinese short video-sharing platforms with the most users, TikTok, Bilibili, and Kwai, were retrieved. The Global Quality Score (GQS) and the modified DISCERN tool were used to assess the quality and content of videos, respectively. Additionally, comparative analyzes of videos based on different sources and common H. pylori issues were also conducted. Results: The median GQS score and DISCERN score was 2 for H. pylori-related videos analyzed in this study. Non-gastroenterologists posted the most H. pylori-related videos (136/242, 56.2%). Videos from gastroenterologists (51/242, 21.0%) had the highest GQS and DISCERN scores, with a median of 3. Few videos had content on family-based H. pylori infection control and management (5.8%), whether all H. pylori-positive patients need to undergo eradication treatment (27.7%), and the adverse effects of H. pylori eradication therapy (16.1%). Conclusion: Generally, the content and quality of the information in H. pylori-related videos were unsatisfactory, and the quality of the video correlated with the source of the video. Videos from gastroenterologists provided more correct guidance with higher-quality information on the prevention and treatment of H. pylori infection.

Characterization and Genomic Analysis of a New Phage Infecting Helicobacter pylori.

Helicobacter pylori, a significant human gastric pathogen, has been demonstrating increased antibiotic resistance, causing difficulties in infection treatment. It is therefore important to develop alternatives or complementary approaches to antibiotics to tackle H. pylori infections, and (bacterio)phages have proven to be effective antibacterial agents. In this work, prophage isolation was attempted using H. pylori strains and UV radiation. One phage was isolated and further characterized to assess potential phage-inspired therapeutic alternatives to H. pylori infections. HPy1R is a new podovirus prophage with a genome length of 31,162 bp, 37.1% GC, encoding 36 predicted proteins, of which 17 were identified as structural. Phage particles remained stable at 37 °C, from pH 3 to 11, for 24 h in standard assays. Moreover, when submitted to an in vitro gastric digestion model, only a small decrease was observed in the gastric phase, suggesting that it is adapted to the gastric tract environment. Together with its other characteristics, its capability to suppress H. pylori population levels for up to 24 h post-infection at multiplicities of infection of 0.01, 0.1, and 1 suggests that this newly isolated phage is a potential candidate for phage therapy in the absence of strictly lytic phages.

Role of TRPV4 in the Diagnosis and Treatment of Helicobacter pylori Infection in Children with Duodenal Ulcers.

Duodenal ulcer seriously affects the quality of life and life safety of children, but the pathogenesis of children with duodenal ulcer is still unclear. As an important second messenger in the body, Ca2+ participates in the physiological and pathological processes of various diseases. Therefore, transient receptor potential vanilloid type 4 (TRPV4) as one of the channels that mediate Ca2+ has attracted widespread attention in recent years. Here, we found that TRPV4 is highly expressed in children with duodenal ulcer and has good diagnostic value through specimens of children with duodenal ulcer, and animal experiments have proved that TRPV4 is also highly expressed in duodenal ulcer mice. In addition, TRPV4 can enhance intestinal permeability, thereby promoting further infiltration of inflammatory factors. In summary, these results indicate that TRPV4 is involved in the occurrence and development of duodenal ulcer. Therefore, this study provides the diagnostic and therapeutic value of TRPV4 in children with duodenal ulcer.

Cross-roads for meta-analysis and network meta-analysis of H. pylori therapy.

Helicobacter pylori infections are responsible for tremendous morbidity and mortality worldwide, leading to efforts to eradicate the organism. However, the effectiveness of antimicrobial therapy has been undermined by the progressive development of antimicrobial resistance. Treatments and treatment guidelines have been based on traditional pairwise meta-analyses of randomised controlled trials. More recently, network meta-analyses have also been used in an attempt to provide useful information to the clinician regarding which therapies appear best and which to avoid as the least efficacious. However, both forms of meta-analysis have been undermined by the same problems including the poor quality of the clinical trials using unoptimised regimens and incomparable comparisons related to marked geographic and ethnic genotypic and phenotypic heterogeneity. In addition, the comparator regimens often consist of invalid strawman comparisons. New approaches concerning H. pylori treatment and analysis of therapies are needed. H. pylori therapies should be based on antimicrobial stewardship, as in other infectious diseases. This approach requires the use of only optimised therapies proven to be reliably highly effective in the local population (eg, a cure rate of >90%) for both the study and the comparator regimens. Meta-analyses should be restricted to regimens that meet these criteria and must take into account the presence of marked geographical and host genetic and phenotypic heterogeneity. In addition, to provide clinically relevant results, treatment outcomes should focus on, and present, actual cure rates in addition to odd ratios.

Dyspepsia Challenge in Primary Care Gastroenterology.

BACKGROUND: The purpose of this review is to take a deep dive into general problems and challenges of diagnosis and treatment of patients with symptoms of dyspepsia in primary care practice. SUMMARY: Primary care physicians become acquainted with a broad range of clinical problems and therefore require a wide span of knowledge in taking care of patients from their first medical examination within the health care system. Dyspepsia and Helicobacter pylori infection are two of the most frequent reasons of digestive-related health care issues, despite that in primary care practice, current recommendations for diagnosis and differential therapy are often not implemented. The "test-and-treat" strategy is the initial management of the condition, reserving gastroscopy for patients refractory to symptomatic treatment and for patients presenting with any of the following alarm signs: age of above 55, dysphagia, anemia, weight loss, frequent vomiting, family history of GI malignancy, or a physical examination with key pathological findings. KEY MESSAGES: Examination and treatment of dyspepsia symptoms is the diagnostic and therapeutic challenge dictated by organizational and economic potentials of the health system, professional resources, and primary health care capabilities to accept and treat patients with dyspepsia and to properly refer those with alarm symptoms and findings indicative of organic disease to a gastroenterologist.

Acupuncture therapy for gastric ulcer: A protocol for systematic review and meta-analysis.

BACKGROUND: Gastric ulcer (GU) is a clinically common disease of the digestive system that adversely affects patients' quality of life and work ability. Although some articles have reported that acupuncture can improve the clinical symptoms of GU, the efficacy of acupuncture has not been scientifically or methodically evaluated. This study aimed to evaluate the effectiveness and safety of acupuncture for the treatment of patients with gastric ulcers. METHODS: The following electronic databases will be searched from the respective dates of database inception to March 23, 2021: The Cochrane Library, Web of Science, EMBASE, MEDLINE, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Wanfang database, the Chinese Scientific Journal Database, and other sources. Randomized controlled trials comparing acupuncture with other interventions or sham acupuncture were included. Two independent researchers will perform article retrieval, duplication removal, screening, quality evaluation, and data analyses by Review Manager (V.5.3.5). Meta-analyzes, subgroup analysis, and/or descriptive analyses will be performed based on the included data conditions. RESULTS: The protocol of this study systematically assessed the effectiveness and safety of acupuncture for gastric ulcer patients. The primary outcome was the effective rate, and the secondary outcomes included negative conversing rate of Helicobacter pylori infection, untoward effect, recurrence rate, quality of life, and symptom scores. CONCLUSION: This study provides evidence of whether acupuncture is an effective and safe intervention for gastric ulcers. PROSPERO REGISTRATION NUMBER: CRD42021251067.

Risk factor, diagnosis, and current treatment of H. pylori Infection in Indonesia: A Literature Review.

Helicobacter pylori (H. pylori) infection has become an emerging problem in Indonesia despite its relatively low prevalence as opposed to other Southeast Asian and Asian countries. Strains containing less virulent genotypes predominantly found in Indonesia is suggested to be the rationale for why the disease prevalence, as well as its gastric cancer complication, remain inferior in respect of neighboring counterparts. Although endoscopic evaluation is still necessary to determine the gastric mucosal status of those infected with H. pylori, the infection itself can be easily diagnosed with test-and-treat strategy especially in areas with limited resources. Several findings revealed high rates of antibiotic resistance varying among Indonesian regions and ethnicities, suggesting that triple therapy regimen may not be suitable for all population. Whereas treatment should be based on the pattern of resistance in respected region, novel regimens involving furazolidone, rifabutin, and sitafloxacin are proposed as potential drugs of choice to eradicate H. pylori infection. In order to determine the adequate approach for H. pylori infection in Indonesia, further multicenter studies involving larger sample size should be conducted.

In Vitro Framework to Assess the Anti-Helicobacter pylori Potential of Lactic Acid Bacteria Secretions as Alternatives to Antibiotics.

Helicobacter pylori is a prevalent bacterium that can cause gastric ulcers and cancers. Lactic acid bacteria (LAB) ameliorate treatment outcomes against H. pylori, suggesting that they could be a source of bioactive molecules usable as alternatives to current antibiotics for which resistance is mounting. We developed an in vitro framework to compare the anti-H. pylori properties of 25 LAB and their secretions against H. pylori. All studies were done at acidic and neutralized pH, with or without urea to mimic various gastric compartments. Eighteen LAB strains secreted molecules that curtailed the growth of H. pylori and the activity was urea-resistant in five LAB. Several LAB supernatants also reduced the urease activity of H. pylori. Pre-treatment of H. pylori with acidic LAB supernatants abrogated its flagella-mediated motility and decreased its ability to elicit pro-inflammatory IL-8 cytokine from human gastric cells, without reverting the H. pylori-induced repression of other pro-inflammatory cytokines. This study identified the LAB that have the most anti-H. pylori effects, decreasing its viability, its production of virulence factors, its motility and/or its ability to elicit pro-inflammatory IL-8 from gastric cells. Once identified, these molecules can be used as alternatives or complements to current antibiotics to fight H. pylori infections.

The interplay between Helicobacter pylori and gastrointestinal microbiota.

The complex population of microbes in the human gastrointestinal (GI) tract interacts with itself and with the host, exerting a deep influence on health and disease development. The development of modern sequencing technology has enabled us to gain insight into GI microbes. Helicobacter pylori colonization significantly affects the gastric microenvironment, which in turn affects gastric microbiota and may be correlated with colonic microbiota changes. Crosstalk between H. pylori and GI commensal flora may play a role in H. pylori-related carcinogenicity and extragastric manifestations. We review current knowledge on how H. pylori shapes GI microbiota with a specific focus on its impact on the stomach and colon. We also review current evidence on colonic microbiota changes attributed to eradication therapy based on the clinical studies performed to date.

Application of Visual Gene Clip-Based Tailored Therapy for the Eradication of Helicobacter pylori.

BACKGROUND: Helicobacter pylori eradication with therapies employing a proton pump inhibitor (PPI) and antimicrobial agents is mainly achieved via bacterial susceptibility to antimicrobial agents and the magnitude of acid secretion inhibition. However, annual eradication rates have greatly declined in Mainland China, and therefore, tailored H. pylori eradication regimens that inhibit acid secretion and employ optimal antimicrobial agents determined based on gene clip testing may improve eradication rates. This study was aimed at evaluating the efficacy of tailored H. pylori eradication therapy guided by visual gene clip testing for antibiotic resistance and PPI metabolism genotypes. METHODS: This prospective study included 244 patients (141 men and 103 women aged 20-79 years) receiving initial treatment for H. pylori infection. Visual gene clip testing using gastric mucosal specimens was performed to detect antibiotic resistance to clarithromycin conferred by the A2142G and A2143G point mutations of the H. pylori 23S rRNA gene and to levofloxacin conferred by the Asn87 and Asp91 point mutations of the H. pylori gyrA gene. Patients received a 14-day bismuth quadruple therapy regimen guided by testing for antibiotic resistance and CYP2C19 polymorphisms, and primary H. pylori eradication was assessed at least 4 weeks after therapy. RESULTS: H. pylori strains were successfully isolated from the gastric mucosa tissues of 244 patients. Antibiotic resistant isolates were identified in 63 patients, with clarithromycin resistance observed in 50 patients, levofloxacin resistance in 7 patients, and dual resistance in 6 patients. The PPI metabolic genotype of CYP2C19 was detected in 242 of 244 cases, and 97 cases were categorized as extensive metabolizers, 141 as intermediate metabolizers, and 4 as poor metabolizers. Among the 242 patients who received tailored therapy, the H. pylori eradication rate was 90.9% (95% confidence interval 87.3%~94.6%) in the intention-to-treat analysis and 96.9% (95% confidence interval 94.7%~99.2%) in the per protocol analysis. CONCLUSIONS: Tailored therapy for H. pylori infection guided by determination of antibiotic resistance and CYP2C19 polymorphism using visual gene chip technology may provide high clinical effectiveness as initial H. pylori eradication therapy.