Pylori Colonization Research Articles

Intranasal immunization with poly I:C and CpG ODN adjuvants enhances the protective efficacy against Helicobacter pylori infection in mice

Helicobacter pylori (H. pylori) infection is a serious public health issue, and development of vaccines is a desirable preventive strategy for H. pylori. Toll-like receptor (TLR) ligands have shown potential as vaccine adjuvants that induce immune responses, but polyinosinic-polycytidylic acid (poly I:C), a nucleic acid-based TLR9 ligand, is less well studied in H. pylori vaccine research. Here, we evaluated the effects of poly I:C and CpG oligodeoxynucleotide (CpG ODN), a nucleic acid TLR3 ligand, as adjuvants in combination with the H. pylori recombinant proteins LpoB and UreA to protect against H. pylori infection. For analysis of specific immune responses, the levels of specific antibodies and splenic cytokines were measured in the immunized mice. Compared with CpG ODN, poly I:C could induce mucosal sIgA antibody responses and reduce H. pylori colonization. Additionally, the combination of poly I:C and CpG ODN caused greater immunoprotection and significantly reduced gastritis, exerting synergistic effects. Analysis of splenic cytokines revealed that poly I:C mainly triggered a mixed Th1/Th2/Th17 immune response, whereas the combination of CpG ODN and poly I:C induced a Th1/Th17 immune response. Our findings indicated that increased levels of mucosal sIgA antibodies and a robust splenic Th1/Th17 immune response were associated with reduced H. pylori colonization in vaccinated mice. This study identified a potential TLR ligand adjuvant for developing more effective H. pylori vaccines.

Oral Live-Carrier Vaccine of Recombinant Lactococcus lactis Inducing Prophylactic Protective Immunity Against Helicobacter pylori Infection.

Helicobacter pylori infects the gastric mucosa and induces chronic gastritis, peptic ulcers, and gastric cancer. Research has demonstrated that vaccination can induce a protective immune response and prevent H. pylori infection. Oral administration of the Lactococcus lactis live-carrier vaccine is safe and easily complied with by the public. In this study, two recombinant L. lactis strains were constructed that expressed antigens of H. pylori urease subunit alpha (UreA) and UreA fused with Escherichia coli heat-labile toxin B subunit (LTB-UreA), named LL-UreA and LL-LTB-UreA, respectively. The expression of antigen proteins was confirmed by Western blotting analysis. Survival assessment indicated that the engineered L. lactis could colonize in the digestive tract of BALB/c mice up to 10 days after the last oral administration with our immunization protocol. The ability to induce immune response and immune protective efficacy of the L. lactis were confirmed. These results indicated that oral administration with LL-UreA or LL-LTB-UreA could induce UreA-specific mucosal secretory IgA (sIgA) and cellular immune response, significantly increasing the cytokines levels of interferon-gamma (IFN-γ), interleukin (IL)-17A, and IL-10, together with the proportion of CD4+IFN-γ+ T cells and CD4+IL17A+ T cells. More importantly, oral administration of LL-UreA and LL-LTB-UreA brought about effective protection in mice to prevent H. pylori infection, especially LL-UreA, resulting in 70% of mice showing no H. pylori colonization and the remaining 30% showing only low levels of colonization. These findings underscore the potential of using orally administered engineered L. lactis vaccines to prevent H. pylori infection.

Association between Helicobacter pylori infection, MASLD, and liver fibrosis in patients with severe obesity: a single-center experience.

Our study sought to evaluate if an association exists between Helicobacter pylori (H. pylori), metabolic dysfunction- associated steatotic liver disease (MASLD), and liver fibrosis in patients with severe obesity (BMI > 35). Our retrospective study included 584 patients over the age of 18years with severe obesity, who underwent preoperative liver transient elastography (VCTE), upper endoscopy, blood work, and intra-operative liver biopsy concurrent with bariatric surgery at a single institution from July 2020 to September 2021. Liver fibrosis scores including FIB-4, APRI, NAFLD fibrosis score, BARD score, AST: ALT ratio, and NAFLD activity score (NAS) were calculated from the laboratory results and liver biopsy findings. The presence or absence of H. pylori was determined based on gastric biopsies obtained during upper endoscopy. Other variables collected included age, gender, mean preoperative weight, BMI, and the presence or absence of comorbidities. Student's t-test and non-parametric testing were used for the analysis of continuous variables and Chi-square analysis was used for categorical data. Of the 584 patients, 14.7% were H. pylori positive and 85.3% were negative. Liver fibrosis scores including FIB-4, APRI, and NAFLD fibrosis scores were significantly higher in the positive group (p < 0.05), but there was no difference in AST: ALT ratio and BARD score. A significantly higher VCTE steatosis and fibrosis scores were noted in the H. pylori-positive group (p < 0.05). Similarly, a significantly higher NAS (NAFLD activity score) on liver biopsies was noted in the positive group, with all the individual components of NAS (steatosis, lobular inflammation, and hepatocyte ballooning) being significantly higher in the positive group (p < 0.05). A significantly higher incidence of fibrosis on liver biopsies was noted in the positive group overall and across all stages of fibrosis (p < 0.05). There were no significant differences between the groups in relation to gender, mean weight, BMI, presence of comorbidities including Diabetes Mellitus, and laboratory values. Our study demonstrates that H. pylori colonization or infection is associated with a higher risk of development of MASLD and progression to fibrosis. Further, population-based studies are needed to corroborate our findings.

High galectin expression in Helicobacter pylori-infected gastric mucosa in childhood

BackgroundMild Th1 and Th17 immune responses in childhood against Helicobacter pylori are presumed to be responsible for H. pylori colonization and mucosal atrophy reduction. However, the mechanism remains unclear. In this study, we aimed to investigate the childhood-specific immune responses observed after H. pylori infection by analyzing galectin expression in the gastric mucosa. We focused on galectin-1 (Gal-1) and galectin-9 (Gal-9), which function to suppress Th1 and Th17 immune responses. MethodsWe analyzed changes in the expression of Gal-1 and Gal-9 in the gastric mucosa of pediatric patients with H. pylori infection. Ten pediatric patients with and ten patients without H. pylori infection who underwent biopsy to assess the cause of chronic abdominal symptoms using esophagogastroduodenoscopy were evaluated. Gal-1 and Gal-9 expression in the biopsy tissues of the gastric antrum and corpus was analyzed by immunohistochemical staining. ResultsGal-1 expression was significantly increased in the stromal cells of the corpus owing to H. pylori infection. No alterations in Gal-1 expression due to H. pylori infection were observed in the antral tissue. Helicobacter pylori infection considerably increased Gal-9 expression in all tissues. According to previous reports, the increased expression of Gal-9 associated with H. pylori infection is not observed in adults. Therefore, the increased expression of Gal-9 associated with H. pylori infection is specific to pediatric patients. ConclusionThe increased expression of Gal-1 and Gal-9 may suppress Th1 and Th17 immune responses against H. pylori infection during childhood, promote H. pylori colonization, and reduce inflammation in the gastric mucosa of pediatric patients.

Indole-3-Lactic Acid Derived from Lacticaseibacillus paracasei Inhibits Helicobacter pylori Infection via Destruction of Bacteria Cells, Protection of Gastric Mucosa Epithelial Cells, and Alleviation of Inflammation.

Indole-3-lactic acid (ILA) has exhibited antimicrobial properties. However, its role in inhibiting Helicobacter pylori infection remains elusive. This study investigated the inhibitory effect of ILA produced by Lacticaseibacillus paracasei on H. pylori, which was further confirmed by cell and animal experiments. 5 mg/mL ILA was sufficient to directly inhibit the growth of H. pylori in vitro, with a urease inhibitory activity reaching 60.94 ± 1.03%, and the cell morphology and structure were destroyed. ILA inhibited 56.5% adhesion of H. pylori to GES-1 and significantly reduced the number of apoptotic cells. Furthermore, ILA suppresses H. pylori colonization by approximately 38% to 63%, reduced inflammation and oxidative stress in H. pylori-infected mice, and enhanced the enrichment and variety of gut microbiota, notably fostering the growth of beneficial bacteria such as Lactobacillus and Bifidobacterium strains. The results support that ILA derived from Lactobacillus can be applicated as a novel prebiotic in anti-H. pylori functional foods.

Screening Probiotics for Anti-Helicobacter pylori and Investigating the Effect of Probiotics on Patients with Helicobacter pylori Infection.

Probiotics are natural microbial agents with beneficial properties such as bacteriostatic and anti-infective properties. Lactobacillus plantarum Q21, Q25 and QA85, were isolated from the Chinese specialty fermented food "Jiangshui" and proved to be highly resistant to Helicobacter pylori (p < 0.0001). In vitro results showed that Q21, Q25 and QA85 strongly inhibited H. pylori and could specifically co-aggregate H. pylori in vitro (more than 56%). Strains have the potential to adhere to cells and hinder H. pylori colonization (p < 0.0001). To assess the anti-H. pylori efficacy of strains in vivo, volunteers were recruited and a self-controlled study of probiotic intervention was conducted. Compared to pre-probiotics, volunteers who took Q21, Q25 and QA85 for 1 month showed significant improvement in discomfort, a significant reduction in GSRS scores (p < 0.05), and modulation of inflammatory response (p < 0.05). Q21, Q25 and QA85 resulted in a decreasing trend of H. pylori load in volunteers (454.30 ± 327.00 vs. 328.35 ± 237.19, p = 0.06). However, the strains were not significantly effective in modulating the imbalance of the gut microbiota caused by H. pylori infection. In addition, strains affect metabolic pathways by increasing the levels of O-Phosphoethanolamine and other related metabolites, which may ameliorate associated symptoms. Therefore, Lactobacillus plantarum Q21, Q25 and QA85 can be regarded as a candidate probiotic preparation that exerts direct or indirect anti-H. pylori effects by inhibiting H. pylori activity and colonization, reducing inflammation and discomfort, maintaining homeostasis in the internal environment, affecting the metabolic pathways and repairing the body barrier. They can play a role in relieving H. pylori infection.

Influence of helicobacter pylori on composition and function of gastric microbiota in patients with chronic non-atrophic gastritis

ObjectiveHelicobacter pylori (H. pylori) plays a major role in causing and advancing gastrointestinal illnesses. Our aim is to analyze the unique makeup and functional changes in the gastric microbiota of patients with chronic non-atrophic gastritis (CNAG), regardless of the presence of H. pylori, and to determine the potential signaling pathways. MethodsWe performed metagenomic sequencing on gastric mucosa samples collected from 17 individuals with non-atrophic gastritis, comprising 6 cases were infected with H. pylori (H. pylori-infected case group) and 11 cases without (control group). The species composition was evaluated with DIAMOND software, and functional enrichment was assessed utilizing the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. We analyzed antibiotic resistance patterns using the Comprehensive Antibiotic Resistance Database as a reference (CARD). ResultsThe presence of H. pylori colonization in CNAG patients was associated with increased diversity in the gastric microbiota. The Phylum Firmicutes was found to be less prevalent, while the Phylum Proteobacteria showed an increase. Functionally, pathways associated with metabolic pathways, including vitamins, auxiliaries, amino acid residue, carbon hydrate, and metabolic energy pathways, were enriched in CNAG patients with H. pylori infection. Additionally, antibiotic resistance genes correlated with antibiotic efflux pump were enriched. ConclusionsFrom a holistic genomic perspective, our findings offer fresh perspectives into the gastric microbiome among CNAG patients carrying H. pylori, which is valuable for future research on CNAG.

Dual RNA sequencing of Helicobacter pylori and host cell transcriptomes reveals ontologically distinct host-pathogen interaction.

Simultaneous profiling of the dynamic interaction between Helicobacter pylori and the human gastric epithelium represents a novel strategy for identifying regulatory responses that drive pathogenesis. This study presents the first dual-transcriptome analysis of H. pylori when cocultured with gastric epithelial cells, revealing a bacterial adaptation strategy and a general repression of electron transportation-associated genes, both of which were modulated by cytotoxin-associated gene A (cagA). Temporal profiling of host mRNA signatures dissected the aberrant pre-mRNA splicing of functional genes involved in the cell cycle process in response to H. pylori infection. We demonstrated a protective effect of gastric H. pylori colonization against chronic DSS-induced colitis through both in vitro and in vivo experiments. These findings significantly enhance our understanding of how H. pylori promotes infection and pathogenesis in the human gastric epithelium and provide evidence to identify targets for antimicrobial therapies.

Recombinant L. lactis vaccine LL-plSAM-WAE targeting four virulence factors provides mucosal immunity against H. pylori infection

BackgroundHelicobacter pylori (H. pylori) causes chronic gastric disease. An efficient oral vaccine would be mucosa-targeted and offer defense against colonization of invasive infection in the digestive system. Proteolytic enzymes and acidic environment in the gastrointestinal tract (GT) can, however, reduce the effectiveness of oral vaccinations. For the creation of an edible vaccine, L. lactis has been proposed as a means of delivering vaccine antigens.ResultsWe developed a plSAM (pNZ8148-SAM) that expresses a multiepitope vaccine antigen SAM-WAE containing Urease, HpaA, HSP60, and NAP extracellularly (named LL-plSAM-WAE) to increase the efficacy of oral vaccinations. We then investigated the immunogenicity of LL-plSAM-WAE in Balb/c mice. Mice that received LL-plSAM-WAE or SAM-WAE with adjuvant showed increased levels of antibodies against H. pylori, including IgG and sIgA, and resulted in significant reductions in H. pylori colonization. Furthermore, we show that SAM-WAE and LL-plSAM-WAE improved the capacity to target the vaccine to M cells.ConclusionsThese findings suggest that recombinant L. lactis could be a promising oral mucosa vaccination for preventing H. pylori infection.

Unraveling the crystal structure of the HpaA adhesin: insights into cell adhesion function and epitope localization of a Helicobacter pylori vaccine candidate.

Helicobacter pylori is a bacterium that can cause chronic gastritis, peptic ulcers, and gastric cancers. The bacterium adheres to the lining of the stomach using proteins called adhesins. One of these proteins, HpaA, is particularly important for H. pylori colonization and is considered a promising vaccine candidate against H. pylori infections. In this work, we determined the atomic structure of HpaA, identifying a characteristic protein fold to the Helicobacter family and delineating specific amino acids that are crucial to support the attachment to the gastric cells. Additionally, we discovered that HpaA can trigger the production of TNF-α, a proinflammatory molecule, in macrophages. These findings provide valuable insights into how H. pylori causes disease and suggest that HpaA has a dual role in both attachment and immune activation. This knowledge could contribute to the development of improved vaccine strategies for preventing H. pylori infections.

Infiltration to infection: key virulence players of Helicobacter pylori pathogenicity.

This study aims to comprehensively review the multifaceted factors underlying the successful colonization and infection process of Helicobacter pylori (H. pylori), a prominent Gram-negative pathogen in humans. The focus is on elucidating the functions, mechanisms, genetic regulation, and potential cross-interactions of these elements. Employing a literature review approach, this study examines the intricate interactions between H. pylori and its host. It delves into virulence factors like VacA, CagA, DupA, Urease, along with phase variable genes, such as babA, babC, hopZ, etc., giving insights about the bacterial perspective of the infection The association of these factors with the infection has also been added in the form of statistical data via Funnel and Forest plots, citing the potential of the virulence and also adding an aspect of geographical biasness tothe virulence factors. The biochemical characteristics and clinical relevance of these factors and their effects on host cells are individually examined, both comprehensively and statistically. H. pylori is a Gram-negative, spiral bacterium that successfully colonises the stomach of more than half of the world's population, causing peptic ulcers, gastric cancer, MALT lymphoma, and other gastro-duodenal disorders. The clinical outcomes of H. pylori infection are influenced by a complex interplay between virulence factors and phase variable genes produced by the infecting strain and the host genetic background. A meta-analysis of the prevalence of all the major virulence factors has also been appended. This study illuminates the diverse elements contributing to H. pylori's colonization and infection. The interplay between virulence factors, phase variable genes, and host genetics determines the outcome of the infection. Despite biochemical insights into many factors, their comprehensive regulation remains an understudied area. By offering a panoramic view of these factors and their functions, this study enhances understanding of the bacterium's perspective, i.e. H. pylori's journey from infiltration to successful establishment within the host's stomach.

LOX-1 acts as an N6-methyladenosine-regulated receptor for Helicobacter pylori by binding to the bacterial catalase.

The role of N6-methyladenosine (m6A) modification of host mRNA during bacterial infection is unclear. Here, we show that Helicobacter pylori infection upregulates host m6A methylases and increases m6A levels in gastric epithelial cells. Reducing m6A methylase activity via hemizygotic deletion of methylase-encoding gene Mettl3 in mice, or via small interfering RNAs targeting m6A methylases, enhances H. pylori colonization. We identify LOX-1 mRNA as a key m6A-regulated target during H. pylori infection. m6A modification destabilizes LOX-1 mRNA and reduces LOX-1 protein levels. LOX-1 acts as a membrane receptor for H. pylori catalase and contributes to bacterial adhesion. Pharmacological inhibition of LOX-1, or genetic ablation of Lox-1, reduces H. pylori colonization. Moreover, deletion of the bacterial catalase gene decreases adhesion of H. pylori to human gastric sections. Our results indicate that m6A modification of host LOX-1 mRNA contributes to protection against H. pylori infection by downregulating LOX-1 and thus reducing H. pylori adhesion.

Solid Lipid Nanoparticles Delivering a DNA Vaccine Encoding Helicobacter pylori Urease A Subunit: Immune Analyses before and after a Mouse Model of Infection.

In this study, novel solid lipid particles containing the adjuvant lipid monophosphoryl lipid A (termed 'SLN-A') were synthesised. The SLN-A particles were able to efficiently bind and form complexes with a DNA vaccine encoding the urease alpha subunit of Helicobacter pylori. The resultant nanoparticles were termed lipoplex-A. In a mouse model of H. pylori infection, the lipoplex-A nanoparticles were used to immunise mice, and the resultant immune responses were analysed. It was found that the lipoplex-A vaccine was able to induce high levels of antigen-specific antibodies and an influx of gastric CD4+ T cells in vaccinated mice. In particular, a prime with lipoplex-A and a boost with soluble UreA protein induced significantly high levels of the IgG1 antibody, whereas two doses of lipoplex-A induced high levels of the IgG2c antibody. In this study, lipoplex-A vaccination did not lead to a significant reduction in H. pylori colonisation in a challenge model; however, these results point to the utility of the system for delivering DNA vaccine-encoded antigens to induce immune responses and suggest the ability to tailor those responses.

Mechanistic research: Selenium regulates virulence factors, reducing adhesion ability and inflammatory damage of Helicobacter pylori.

The pathogenicity of Helicobacter pylori is dependent on factors including the environment and the host. Although selenium is closely related to pathogenicity as an environmental factor, the specific correlation between them remains unclear. To investigate how selenium acts on virulence factors and reduces their toxicity. H. pylori strains were induced by sodium selenite. The expression of cytotoxin-associated protein A (CagA) and vacuolating cytotoxin gene A (VacA) was determined by quantitative PCR and Western blotting. Transcriptomics was used to analyze CagA, CagM, CagE, Cag1, Cag3, and CagT. C57BL/6A mice were infected with the attenuated strains subjected to sodium selenite induction, and H. pylori colonization, inflammatory reactions, and the cell adhesion ability of H. pylori were assessed. CagA and VacA expression was upregulated at first and then downregulated in the H. pylori strains after sodium selenite treatment. Their expression was significantly and steadily downregulated after the 5th cycle (10 d). Transcriptome analysis revealed that sodium selenite altered the levels affect H. pylori virulence factors such as CagA, CagM, CagE, Cag1, Cag3, and CagT. Of these factors, CagM and CagE expression was continuously downregulated and further downregulated after 2 h of induction with sodium selenite. Moreover, CagT expression was upregulated before the 3rd cycle (6 d) and significantly downregulated after the 5th cycle. Cag1 and Cag3 expression was upregulated and downregulated, respectively, but no significant change was observed by the 5th cycle. C57BL/6A mice were infected with the attenuated strains subjected to sodium selenite induction. The extent of H. pylori colonization in the stomach increased; however, sodium selenite also induced a mild inflammatory reaction in the gastric mucosa of H. pylori-infected mice, and the cell adhesion ability of H. pylori was significantly weakened. These results demonstrate that H. pylori displayed virulence attenuation after the 10th d of sodium selenite treatment. Sodium selenite is a low toxicity compound with strong stability that can reduce the cell adhesion ability of H. pylori, thus mitigating the inflammatory damage to the gastric mucosa.

The Helicobacter pylori methylome is acid-responsive due to regulation by the two-component system ArsRS and the type I DNA methyltransferase HsdM1 (HP0463).

In addition to its role in genome protection, DNA methylation can regulate gene expression. In this study, we characterized the impact of acidity, phase variation, and the ArsRS TCS on the expression of the Type I m6A DNA methyltransferase HsdM1 (HP0463) of Helicobacter pylori 26695 and their subsequent effects on the methylome. Transcription of hsdM1 increases at least fourfold in the absence of the sensory histidine kinase ArsS, the major acid-sensing protein of H. pylori. hsdM1 exists in the phase-variable operon hsdR1-hsdM1. Phase-locking hsdR1 (HP0464), the restriction endonuclease gene, has significant impacts on the transcription of hsdM1. To determine the impacts of methyltransferase transcription patterns on the methylome, we conducted methylome sequencing on samples cultured at pH 7 or pH 5. We found differentially methylated motifs between these growth conditions and that deletions of arsS and/or hsdM1 interfere with the epigenetic acid response. Deletion of arsS leads to altered activity of HsdM1 and multiple other methyltransferases under both pH conditions indicating that the ArsRS TCS, in addition to direct effects on regulon transcription during acid acclimation, may also indirectly impact gene expression via regulation of the methylome. We determined the target motif of HsdM1 (HP0463) to be the complementary bipartite sequence pair 5'-TCAm6AVN6TGY-3' and 3'-AGTN6GAm6ACA-5'. This complex regulation of DNA methyltransferases, and thus differential methylation patterns, may have implications for the decades-long persistent infection by H. pylori. IMPORTANCE This study expands the possibilities for complex, epigenomic regulation in Helicobacter pylori. We demonstrate that the H. pylori methylome is plastic and acid sensitive via the two-component system ArsRS and the DNA methyltransferase HsdM1. The control of a methyltransferase by ArsRS may allow for a layered response to changing acidity. Likely, an early response whereby ArsR~P affects regulon expression, including the methyltransferase hsdM1. Then, a somewhat later effect as the altered methylome, due to altered HsdM1 expression, subsequently alters the expression of other genes involved in acclimation. The intermediate methylation of certain motifs supports the hypothesis that methyltransferases play a regulatory role. Untangling this additional web of regulation could play a key role in understanding H. pylori colonization and persistence.

Helicobacter pylori-Induced Angiopoietin-Like 4 Promotes Gastric Bacterial Colonization and Gastritis.

Helicobacter pylori infection is characterized as progressive processes of bacterial persistence and chronic gastritis with features of infiltration of mononuclear cells more than granulocytes in gastric mucosa. Angiopoietin-like 4 (ANGPTL4) is considered a double-edged sword in inflammation-associated diseases, but its function and clinical relevance in H. pylori-associated pathology are unknown. Here, we demonstrate both pro-colonization and pro-inflammation roles of ANGPTL4 in H. pylori infection. Increased ANGPTL4 in the infected gastric mucosa was produced from gastric epithelial cells (GECs) synergistically induced by H. pylori and IL-17A in a cagA-dependent manner. Human gastric ANGPTL4 correlated with H. pylori colonization and the severity of gastritis, and mouse ANGPTL4 from non-bone marrow-derived cells promoted bacteria colonization and inflammation. Importantly, H. pylori colonization and inflammation were attenuated in Il17a -/-, Angptl4 -/-, and Il17a -/- Angptl4 -/- mice. Mechanistically, ANGPTL4 bound to integrin αV (ITGAV) on GECs to suppress CXCL1 production by inhibiting ERK, leading to decreased gastric influx of neutrophils, thereby promoting H. pylori colonization; ANGPTL4 also bound to ITGAV on monocytes to promote CCL5 production by activating PI3K-AKT-NF-κB, resulting in increased gastric influx of regulatory CD4+ T cells (Tregs) via CCL5-CCR4-dependent migration. In turn, ANGPTL4 induced Treg proliferation by binding to ITGAV to activate PI3K-AKT-NF-κB, promoting H. pylori-associated gastritis. Overall, we propose a model in which ANGPTL4 collectively ensures H. pylori persistence and promotes gastritis. Efforts to inhibit ANGPTL4-associated pathway may prove valuable strategies in treating H. pylori infection.

Characterization, mechanism and in vivo validation of Helicobacter pylori antagonism by probiotics screened from infants' feces and oral cavity.

Helicobacter pylori (H. pylori) infection is a major cause of chronic gastritis, intestinal metaplasia, and gastric carcinoma. Antibiotics, the conventional regimen for eliminating H. pylori, cause severe bacterial resistance, gut dysbiosis and hepatic insufficiency. Here, fifty lactic acid bacteria (LAB) were initially screened out of 266 strains obtained from infants' feces and oral cavity. The antagonistic properties of these 50 strains against H. pylori were investigated. Based on eight metrics combined with principal component analysis, three LAB with probiotic function and excellent anti-H. pylori capacity were affirmed. Combining dynamics test, metabolite assays, adhesion assays, co-cultivation experiments, and SEM and TEM observations, LAB were found to antagonize H. pylori by causing coccoid conversion and intercellular adhesion. Furthermore, it was found that LAB antagonized H. pylori by four pathways, i.e., production of anti-H. pylori substances, inhibition of H. pylori colonization, enhancement of the gastric mucosal barrier, and anti-inflammatory effect. In addition, animal model experiments verified that the final screened superior strain L. salivarius NCUH062003 had anti-H. pylori activity in vivo. LAB also reduced IL-8 secretion, ultimately alleviating the inflammatory response of gastric mucosa. Whole genome sequencing (WGS) data showed that the NCUH062003 genome contained the secondary metabolite biosynthesis gene cluster T3PKS. Furthermore, NCUH062003 had a strong energy metabolism and substance transport capacity, and produced a small molecule heat stable peptide (SHSP, 4.1-6.5 kDa). Meanwhile, LAB proved to be safe through antibiotic susceptibility testing and CARD database comparisons.

Shaoyao Gancao Decoction Mitigates Helicobacter Pylori-Induced Chronic Atrophic Gastritis by Suppressing MAOB.

Helicobacter pylori (H. pylori) plays an important role in chronic atrophic gastritis (CAG). Interestingly, Shaoyao Gancao decoction (SGD), a traditional Chinese analgesic prescription, has the efficacy of relaxing spasms and relieving pain. Here, we aimed to identify whether SGD alleviates CAG and the underlying mechanism. A CAG mouse model was developed using H. pylori colonization and a high-salt diet. Histological staining was used to study the histopathological damage changes, and RT-qPCR assays the production of inflammatory responses in the gastric mucosa of mice. H. pylori and a high-salt diet induced gastric mucosal damage and apoptosis of gastric mucosal epithelial cells in mice, eliciting a significant inflammatory response. Treatment with SGD alleviated CAG-induced gastric mucosal damage, reduced apoptosis of gastric mucosal epithelial cells, and inhibited the inflammatory response. Bioinformatics was then used to construct the pharmacological network of SGD to explore its potential targets. SGD inhibited inflammatory response in mice with CAG by suppressing the expression of MAOB. Overexpression of MAOB impaired the therapeutic effect of SGD on inflammation in mice with CAG. Collectively, our findings indicated that SGD has the potential to alleviate CAG via downregulating MAOB.

Роль генетически детерминированного дефицита лектинового пути активации комплемента при хронической инфекции Helicobacter pylori у детей

Aim. To study the association of six polymorphic regions of MBL2 (rs11003125, rs7096206, rs7095891, rs1800450, rs1800451, rs5030737), two regions of FCN2 (rs7851696, rs17549193) and one region of MASP2 (rs72550870) with Helicobacter pylori infection and the severity of neutrophilic inflammation in gastric mucosa among children with recurrent abdominal pain. Design. Genetic association study of single nucleotide polymorphisms, case — control type. Materials and methods. 96 adolescents aged 12–17 years with recurrent abdominal pain were examined. Medical history, general clinical methods and fibrogastroscopy with a biopsy of the gastric mucosa were included in the medical testing. Biopsy samples were recorded and processed to assess the neutrophil infiltration and the presence of H. pylori. The results were interpreted according to the Sydney System of Gastritis Classification. Genotyping of allelic gene variants was carried out using real-time polymerase chain reaction (MBL2, MASP2), as well as the restriction analysis of amplification products of specific genome regions (MBL2, FCN2). Results. A high rate of H. pylori colonization was associated with a high frequency of the L allele of the rs11003125 gene polymorphism of the MBL2 gene and with a decrease in the proportion of high MBL — expressing genotypes. Carriage of the Q allele of the rs7095891 gene polymorphism of the MBL2 gene was associated with less pronounced neutrophilic infiltration, and a high frequency of the T allele of the rs7851696 gene polymorphism of the FCN2 gene was associated with severe neutrophilic inflammation in gastric mucosa. No differences in the distribution of MASP2 genotypes were found. Conclusion. The results obtained suggest that genetic defects in the production of MBL and ficolin-2 may cause chronic helicobacteriosis in children and more severe inflammation of gastric mucosa. Further study of these proteins seems to be promising for new approaches to the treatment and prevention of H. pylori complications in children to be identified. Keywords: Helicobacter pylori, mannose-binding lectin, ficolin, MASP, gene polymorphism.

Reassessing the Standard Chemotaxis Framework for Understanding Biased Migration in Helicobacter pylori.

Helicobacter pylori infections are a major cause of peptic ulcers and gastric cancers. The development of robust inflammation in response to these flagellated, motile bacteria is correlated with poor prognosis. Chemotaxis plays a crucial role in H. pylori colonization, enabling the bacteria to swim toward favorable chemical environments. Unlike the model species of bacterial chemotaxis, Escherichia coli, H. pylori cells possess polar flagella. They run forward by rotating their flagella counterclockwise, whereas backward runs are achieved by rotating their flagella clockwise. We delve into the implications of certain features of the canonical model of chemotaxis on our understanding of biased migration in polarly flagellated bacteria such as H. pylori. In particular, we predict how the translational displacement of H. pylori cells during a backward run could give rise to chemotaxis errors within the canonical framework. Also, H. pylori lack key chemotaxis enzymes found in E. coli, without which sensitive detection of ligands with a wide dynamic range seems unlikely. Despite these problems, H. pylori exhibit robust ability to migrate toward urea-rich sources. We emphasize various unresolved questions regarding the biophysical mechanisms of chemotaxis in H. pylori, shedding light on potential directions for future research. Understanding the intricacies of biased migration in H. pylori could offer valuable insights into how pathogens breach various protective barriers in the human host.