Stomach as the target organ of Rickettsia heilongjiangensis infection in C57BL/6 mice identified by click chemistry.

Spotted fever group rickettsiae (SFGR) are obligate intracellular bacteria that cause spotted fever. The limitations of gene manipulation pose great challenges to studying the infection mechanisms of Rickettsia. By combining bioorthogonal metabolism and click chemistry, we developed a method to label R. heilongjiangensis via azide moieties and achieved rapid pathogen localization without complex procedures. Moreover, we constructed a C57BL/6 mice infection model by simulating tick bites and discovered that the stomach is the target organ of R. heilongjiangensis infection through in vivo imaging systems, which explained the occurrence of gastrointestinal symptoms following R. heilongjiangensis infection in some cases. This study offers a unique perspective for subsequent investigations into the pathogenic mechanisms of SFGR and identifies a potential target organ for R. heilongjiangensis.

HtrA-Dependent E-Cadherin Shedding Impairs the Epithelial Barrier Function in Primary Gastric Epithelial Cells and Gastric Organoids.

Impaired E-cadherin (Cdh1) functions are closely associated with cellular dedifferentiation, infiltrative tumor growth and metastasis, particularly in gastric cancer. The class-I carcinogen Helicobacter pylori (H. pylori) colonizes gastric epithelial cells and induces Cdh1 shedding, which is primarily mediated by the secreted bacterial protease high temperature requirement A (HtrA). In this study, we used human primary epithelial cell lines derived from gastroids and mucosoids from different healthy donors to investigate HtrA-mediated Cdh1 cleavage and the subsequent impact on bacterial pathogenesis in a non-neoplastic context. We found a severe impairment of Cdh1 functions by HtrA-induced ectodomain cleavage in 2D primary cells and mucosoids. Since mucosoids exhibit an intact apico-basal polarity, we investigated bacterial transmigration across the monolayer, which was partially depolarized by HtrA, as indicated by microscopy, the analyses of the transepithelial electrical resistance (TEER) and colony forming unit (cfu) assays. Finally, we investigated CagA injection and observed efficient CagA translocation and tyrosine phosphorylation in 2D primary cells and, to a lesser extent, similar effects in mucosoids. In summary, HtrA is a crucially important factor promoting the multistep pathogenesis of H. pylori in non-transformed primary gastric epithelial cells and organoid-based epithelial models.

Gastric microbiota transplantation as a potential treatment for immune checkpoint inhibitor-associated gastritis.

Immune-related adverse events (irAEs) are complications of the use of immune checkpoint inhibitors (ICIs). ICI-associated gastritis is one of the main irAEs. The gastric microbiota is often related to the occurrence and development of many gastric diseases. Gastric microbiota adjustment may be used to treat gastric disorders in the future. Faecal microbiota transplantation can alter the gut microbiota of patients and has been used for treating ICI-associated colitis. Therefore, we propose gastric microbiota transplantation as a supplementary treatment for patients with ICI-associated gastritis who do not respond well to conventional therapy.

Gastric microbiome composition in obese patients and normal weight subjects with functional dyspepsia.

INTRODUCTION: Despite the numerous studies demonstrating gut microbiota dysbiosis in obese subjects, there is no data on the association between obesity and gastric microbiota. The aim of this study was to address this gap in literature by comparing the composition of gastric microbiota in obese patients and a control group which included normal weight volunteers diagnosed with functional dyspepsia (FD). METHODOLOGY: A total of 19 obese patients, and 18 normal weight subjects with FD and normal endoscopy results were included in the study. The gastric tissue samples were collected from participants in both groups by bariatric surgery and endoscopy, respectively, and profiled using 16S ribosomal RNA gene sequencing. RESULTS: There was no significant difference in the α-diversity scores, while distinct gastric microbial compositions were detected in both groups. Significantly lower levels of Bacteroidetes and Fusobacteria, and higher Firmicutes/Bacteroidetes ratio were recorded in the obese patients. A total of 15 bacterial genera exhibited significant difference in gastric abundance with Prevotella_7, Veillonella, Cupriavidus, and Acinetobacter, present in frequencies higher than 3% in at least one subject group. CONCLUSIONS: Our study suggests a significant association between obesity and gastric microbiome composition. Future studies with larger sample size and gastric samples from subjects without any gastrointestinal complications are required to confirm our conclusions.

Gastric bezoars secondary to mixed infection with Sarcina ventriculi and G + bacilli: a case report.

Sarcina ventriculi is a bacterium with a specific histological morphology and infection can present with symptoms such as abdominal pain, nausea, vomiting and occasionally fatal complications. Delayed gastric emptying is regarded as the most significant risk factor for infection. Its pathogenicity is currently unknown and treatment options are inconsistent. Here we report a case of gastric bezoars secondary to a mixed infection of Sarcina ventriculi and G + bacilli, which is diagnosed by a pathological biopsy.

Increasing correlation between oral and gastric microbiota during gastric carcinogenesis.

BACKGROUND/AIMS: Recent research has increasingly focused on the role of the gastric microbiome in the development of gastric cancer. We aimed to investigate the changes in the microbiome during gastric carcinogenesis in structural and functional aspects, with a specific focus on the association between oral and gastric microbiomes. METHODS: We collected saliva, gastric juice, and gastric tissue samples from 141 patients at different stages of gastric carcinogenesis and processed them for microbiome analysis using 16S rRNA gene profiling. The alpha and beta diversities were analyzed, and the differences in microbiome composition and function profiles were analyzed among the groups, as well as the correlation between changes in the oral and gastric microbiomes during carcinogenesis. RESULTS: We observed significant differences in microbial diversity and composition between the disease and control groups, primarily in the gastric juice. Specific bacterial strains, including Schaalia odontolytica, Streptococcus cristatus, and Peptostreptococcus stomatis, showed a significant increase in abundance in the gastric juice in the low-grade dysplasia and gastric cancer groups. Notably, the correlation between the oral and gastric microbiota compositions, increased as the disease progressed. Predictive analysis of the metagenomic functional profiles revealed changes in functional pathways that may be associated with carcinogenesis (ABC transport and two-component systems). CONCLUSION: During gastric carcinogenesis, the abundance of oral commensals associated with cancer increased in the stomach. The similarity in microbial composition between the stomach and oral cavity also increased, implying a potential role of oral-gastric bacterial interactions in gastric cancer development.

Unveiling the Bacterial Community across the Stomach, Hepatopancreas, Anterior Intestine, and Posterior Intestine of Pacific Whiteleg Shrimp.

The gastrointestinal (GI) tract of shrimp, which is comprised of the stomach, hepatopancreas, and intestine, houses microbial communities that play crucial roles in immune defense, nutrient absorption, and overall health. While the intestine's microbiome has been well-studied, there has been limited research investigating the stomach and hepatopancreas. The present study addresses this gap by profiling the bacterial community in these interconnected GI segments of Pacific whiteleg shrimp. To this end, shrimp samples were collected from a local aquaculture farm in South Korea, and 16S rRNA gene amplicon sequencing was performed. The results revealed significant variations in bacterial diversity and composition among GI segments. The stomach and hepatopancreas exhibited higher Proteobacteria abundance, while the intestine showed a more diverse microbiome, including Cyanobacteria, Actinobacteria, Bacteroidetes, Firmicutes, Chloroflexi, and Verrucomicrobia. Genera such as Oceaniovalibus, Streptococcus, Actibacter, Ilumatobacter, and Litorilinea dominated the intestine, while Salinarimonas, Sphingomonas, and Oceaniovalibus prevailed in the stomach and hepatopancreas. It is particularly notable that Salinarimonas, which is associated with nitrate reduction and pollutant degradation, was prominent in the hepatopancreas. Overall, this study provides insights into the microbial ecology of the Pacific whiteleg shrimp's GI tract, thus enhancing our understanding of shrimp health with the aim of supporting sustainable aquaculture practices.

Ability of Helicobacter pylori to internalize into Candida.

The following are our views regarding the "letter to the editor" (Helicobacter is preserved in yeast vacuoles! Does Koch's postulates confirm it?) by Alipour and Gaeini, and the response "letter to the editor" (Candida accommodates non-culturable Helicobacter pylori in its vacuole-Koch's postulates aren't applicable) by Siavoshi and Saniee. Alipour and Gaeini rejected the methods, results, discussion, and conclusions summarized in a review article by Siavoshi and Saniee. The present article reviews and discusses evidence on the evolutionary adaptation of Helicobacter pylori (H. pylori) to thrive in Candida cell vacuoles and concludes that Candida could act as a Trojan horse, transporting potentially infectious H. pylori into the stomach of humans.

Evidence of Helicobacter pylori heterogeneity in human stomachs by susceptibility testing and characterization of mutations in drug-resistant isolates.

Heterogeneity of Helicobacter pylori communities contributes to its pathogenicity and diverse clinical outcomes. We conducted drug-susceptibility tests using four antibiotics, clarithromycin (CLR), amoxicillin (AMX), metronidazole and sitafloxacin, to examine H. pylori population diversity. We also analyzed genes associated with resistance to CLR and AMX. We examined multiple isolates from 42 Japanese patients, including 28 patients in whom primary eradication with CLR and AMX had failed, and 14 treatment-naïve patients. We identified some patients with coexistence of drug resistant- and sensitive-isolates (drug-heteroR/S-patients). More than 60% of patients were drug-heteroR/S to all four drugs, indicating extensive heterogeneity. For the four drugs except AMX, the rates of drug-heteroR/S-patients were higher in treatment-naïve patients than in primary eradication-failure patients. In primary eradication-failure patients, isolates multi-resistant to all four drugs existed among other isolates. In primary eradication-failure drug-heteroR/S-patients, CLR- and AMX-resistant isolates were preferentially distributed to the corpus and antrum with different minimum inhibitory concentrations, respectively. We found two mutations in PBP1A, G591K and A480V, and analyzed these in recombinants to directly demonstrate their association with AMX resistance. Assessment of multiple isolates from different stomach regions will improve accurate assessment of H. pylori colonization status in the stomach.

Microbiota in different digestive tract of paddlefish (Polyodon spathula) are related to their functions.

Paddlefish has high economic and ecological value. In this study, microbial diversity and community structure in intestine, stomach, and mouth of paddlefish were detected using high-throughput sequencing. The results showed that the diversity and richness indices decreased along the digestive tract, and significantly lower proportion of those were observed in intestine. Firmicutes, Bacteroidetes and Proteobacteria were the dominant phyla. In top 10 phyla, there was no significant difference in mouth and stomach. But compared with intestine, there were significant differences in 8 of the 10 phyla, and Firmicutes and Bacteroidetes increased significantly, while Proteobacteria decreased significantly. There was no dominant genus in mouth and stomach, but Clostridium_sensu_stricto_1 and uncultured_bacterium_o_Bacteroidales was predominant in intestine. In conclusion, the species and abundance of microbiota in the mouth and stomach of paddlefish were mostly the same, but significantly different from those in intestine. Moreover, there was enrichment of the dominant bacteria in intestine.

Ottowia cancrivicina sp. nov., isolated from human stomach.

A Gram-negative, facultative anaerobic, non-motile and rod-shaped bacterium, designated 10c7w1T, was isolated from a human gastrointestinal tract. Colonies on agar plates were small, circular, smooth and beige. The optimal growth conditions were determined to be 37 °C, pH 7.0-7.5 and 0 % (w/v) NaCl. Comparative analysis of complete 16S rRNA gene sequences revealed that strain 10c7w1T showed the highest sequence similarity of 95.8 % to Ottowia beijingensis MCCC 1A01410T, followed by Ottowia thiooxydans (95.2 %) JCM 11629T. The average amino acid identity values between 10c7w1T and O. beijingensis MCCC 1A01410T and O. thiooxydans JCM 11629T were above 60 % (71.4 and 69.5 %). The average nucleotide identity values between strain 10c7w1T and O. beijingensis MCCC 1A01410T and O. thiooxydans JCM 11629T were 76.9 and 72.5 %, respectively. The dominant fatty acids (≥10 %) were straight chain ones, with summed feature 3 (C16 : 1 ω7c/C16 : 1 ω6c), summed feature 8 (C18 : 1 ω7c/C18 : 1 ω6c) and C16 : 00 being the most abundant. Q-8 was the only respiratory quinone. The major polar lipids of strain 10c7w1T were phosphatidylethanolamine, diphosphatidylglycerol and unknown lipids. The DNA G+C content of strain 10c7w1T was 63.6 mol%. On the basis of phylogenetic, phenotypic and chemotaxonomic data, strain 10c7w1T is considered to represent a novel species within the genus Ottowia, for which the name Ottowia cancrivicina sp. nov. is proposed. The type strain is 10c7w1T (=MCCC 1H01399T=KCTC 92200T).

Comparison of gastric inflammation and metaplasia induced by Helicobacter pylori or Helicobacter felis colonization in mice.

Gastric cancer is the fifth most diagnosed cancer in the world. Infection by the bacteria Helicobacter pylori (HP) is associated with approximately 75% of gastric cancer cases. HP infection induces chronic gastric inflammation, damaging the stomach and fostering carcinogenesis. Most mechanistic studies on gastric cancer initiation are performed in mice and utilize either mouse-adapted strains of HP or the natural mouse pathogen Helicobacter felis (HF). Here, we identified the differences in gastric inflammation, atrophy, and metaplasia associated with HP and HF infection in mice. PMSS1 HP strain or the CS1 HF strain were co-cultured with mouse peritoneal macrophages to assess their immunostimulatory effects. HP and HF induced similar cytokine production from cultured mouse peritoneal macrophages revealing that both bacteria exhibit similar immunostimulatory effects in vitro. Next, C57BL/6J mice were infected with HP or HF and were assessed 2 months post-infection. HP-infected mice caused modest inflammation within both the gastric corpus and antrum, and did not induce significant atrophy within the gastric corpus. In contrast, HF induced significant inflammation throughout the gastric corpus and antrum. Moreover, HF infection was associated with significant atrophy of the chief and parietal cell compartments and induced the expression of pyloric metaplasia (PM) markers. HP is poorly immunogenic compared to HF. HF induces dramatic CD4+ T cell activation, which is associated with increased gastric cancer risk in humans. Thus, HP studies in mice are better suited for studies on colonization, while HF is more strongly suited for studies on the effects of gastric inflammation on tumorigenesis. . IMPORTANCE: Mouse infection models with Helicobacter species are widely used to study Helicobacter pathogenesis and gastric cancer initiation. However, Helicobacter pylori is not a natural mouse pathogen, and mouse-adapted H. pylori strains are poorly immunogenic. In contrast, Helicobacter felis is a natural mouse pathogen that induces robust gastric inflammation and is often used in mice to investigate gastric cancer initiation. Although both bacterial strains are widely used, their disease pathogenesis in mice differs dramatically. However, few studies have directly compared the pathogenesis of these bacterial species in mice, and the contrasting features of these two models are not clearly defined. This study directly compares the gastric inflammation, atrophy, and metaplasia development triggered by the widely used PMSS1 H. pylori and CS1 H. felis strains in mice. It serves as a useful resource for researchers to select the experimental model best suited for their studies.

Validation of gavage sampling as tool for longitudinal sampling of microbiota of the mouse gastric lumen.

BACKGROUND: Fecal samples are commonly used for longitudinal studies of the gut lumen microbiome to track the course of response to infection or drug treatment, but no comparable method has been evaluated for longitudinal analysis of the gastric lumen microbiome in mice. Herein, a buffer flush of the stomach with a flexible gavage needle was used to collect gastric contents at one or several time points without harming the mouse. These samples were compared to samples collected by sacrifice and dissection of the mouse stomach. Microbiota from these samples were sequenced and evaluated in two ways: the composition of samples as measured by beta diversity and the richness of samples as measured by alpha diversity. Additionally, the effect of multiple sampling every two days on these metrics were studied. DNA was extracted from each of these samples and Illumina 16S rRNA gene sequencing was performed. RESULTS: First, taxonomic richness of gavage and dissection samples was compared. A greater number of taxa was detected in gavage samples than in dissection samples. Second, taxonomic richness was analyzed over time. No significant difference in taxonomic richness was observed with repeated gavage flushes. Third, a comparison was made of the taxonomic composition of samples collected by gavage versus dissection followed by a comparison of samples collected over multiple samplings. Nonmetric multidimensional scaling analysis revealed no clear differences between collection by gavage flushing or dissection. Using weighted Unifrac and Aitchison taxonomic distances between gavage and dissection samples were not significantly different from distances between gavage samples themselves, and no significant difference was found in the taxonomic composition of mice which were sampled repeatedly. Finally, relative abundances of specific identified taxa were compared, and eleven taxa were found to differ in frequency between collection methods. Using the more stringent Analysis of Composition of Microbiomes (ANCOM), seven was found to differ. Similarly, no significant differences were uncovered using these analyses over multiple samples by gastric flush. CONCLUSION: In summary, the consistency of the microbiota collected by gastric flushing recommends its use for microbiome analysis of gastric fluid similar to the use of fecal sampling to study the gut lumen microbiome.

Are there new biomarkers of the gastroduodenal microbiota useful in the diagnosis of coeliac disease in children? A pilot study.

The changing of microbiome could precede the development of coeliac disease (CeD). We compared the bacterial profile of microbiota of tissues collected simultaneously from the stomach and duodenum in newly diagnosed patients with CeD. Biopsies were collected from 60 children and adolescents aged 2-18 years: (1) 40 patients with CeD; (2) 20 children as control group. The evaluation of the bacterial microbiota was carried out by sequencing the V3-V4 regions of the 16S rRNA subunit, using next-generation sequencing (NGS). The composition of bacterial microbiota was correlated with clinical and blood parameters. The beta diversity analysis revealed a significant dissimilarity in the gastric samples between the CeD and control group (Bray-Curtis index, P = 0.008, and weighted UniFrac distance, P = 0.024). At L2 (phylum level), Campylobacterota was only present in the stomach of the CeD group. A comparison of the abundance of bacteria between the stomach and duodenum showed significant differences in 10 OTUs (operational taxonomic units) in the control and 9 OTUs in the CeD group at L6 (genus) and in 8 OTUs and in 6 OTUs, respectively, at L7 (species). A significant correlation was observed between the genus Novosphingobium in stomach of CeD group and possession of the DQ2.5 and DQ 8 allele, and in the duodenum - between the DQ 8 allele and the species Blautia wexlerae. Significant differences in selected, little-known genera of bacteria suggest their potential role as new biomarkers in the development of CeD. To fully understand the mechanism of CeD development in genetically predisposed individuals, it is necessary to take into account not only the abundance of a given genus or species of bacteria, but also the anatomical location of its occurrence.

Effects of Helicobacter pylori infection on intestinal microbiota, immunity and colorectal cancer risk.

Infecting about half of the world´s population, Helicobacter pylori is one of the most prevalent bacterial infections worldwide and the strongest known risk factor for gastric cancer. Although H. pylori colonizes exclusively the gastric epithelium, the infection has also been associated with various extragastric diseases, including colorectal cancer (CRC). Epidemiological studies reported an almost two-fold increased risk for infected individuals to develop CRC, but only recently, direct causal and functional links between the chronic infection and CRC have been revealed. Besides modulating the host intestinal immune response, H. pylori is thought to increase CRC risk by inducing gut microbiota alterations. It is known that H. pylori infection not only impacts the gastric microbiota at the site of infection but also leads to changes in bacterial colonization in the distal large intestine. Considering that the gut microbiome plays a driving role in CRC, H. pylori infection emerges as a key factor responsible for promoting changes in microbiome signatures that could contribute to tumor development. Within this review, we want to focus on the interplay between H. pylori infection, changes in the intestinal microbiota, and intestinal immunity. In addition, the effects of H. pylori antibiotic eradication therapy will be discussed.

The shapeshifting Helicobacter pylori: From a corkscrew to a ball.

There is growing evidence that bacterial morphology is closely related to their lifestyle. The helical Helicobacter pylori relies on its unique shape for survival and efficient colonization of the human stomach. Yet, they have been observed to transform into another distinctive morphology, the spherical coccoid. Despite being hypothesized to be involved in the persistence and transmission of this species, years of effort in deciphering the roles of the coccoid form remain fruitless since contrasting observations regarding its lifestyle were reported. Here, we discuss the two forms of H. pylori with a focus on the coccoid form, the molecular mechanism behind its morphological transformation, and experimental approaches to further develop our understanding of this phenomenon. We also propose a putative mechanism of the coccoid formation in H. pylori through induction of a type-I toxin-antitoxin (TA) system recently shown to influence the morphology of this species.

Essential role of Helicobacter pylori apolipoprotein N-acyltransferase (Lnt) in stomach colonization.

Bacterial lipoproteins are post-translationally modified with acyl chains, anchoring these proteins to bacterial membranes. In Gram-negative bacteria, three enzymes complete the modifications. Lgt (which adds two acyl chains) and LspA (which removes the signal peptide) are essential. Lnt (which adds a third acyl chain) is not essential in certain bacteria including Francisella tularensis, Neisseria gonorrhoeae, and Acinetobacter baumannii. Deleting lnt results in mild to severe physiologic changes. We previously showed lnt is not essential for Helicobacter pylori growth in vitro. Here, the physiologic consequences of deleting lnt in H. pylori and the role of Lnt in the host response to H. pylori were examined using in vitro and in vivo models. Comparing wild-type, Δlnt, and complemented mutant H. pylori, no changes in growth rates or sensitivity to acid or antibiotics were observed. Since deleting lnt changes the number of acyl chains on lipoproteins and the number of acyl chains on lipoproteins impacts the innate immune response through Toll-like receptor 2 (TLR2) signaling, primary human gastric epithelial cells were treated with a purified lipoprotein from wild-type or lnt mutant H. pylori. Differential gene expression analysis indicated that lipoprotein from the lnt mutant induced a more robust TLR2 response. In a complementary approach, we infected wild-type and Tlr2-/- mice and found that both the wild-type and complemented mutant strains successfully colonized the animals. However, the lnt mutant strain was unable to colonize either mouse strain. These results show that lnt is essential for H. pylori colonization and identifies lipoprotein synthesis as a target for therapeutic intervention.

Surviving stomach bugs in UK ethnic groups: a qualitative study.

BACKGROUND: The exposure patterns across ethnic groups are unclear for stomach bugs that cause self-limiting symptoms, significantly burdening UK health-care services and the economy. This study seeks to fill this gap by exploring how inequalities arise in managing stomach bugs in UK ethnic groups. METHODS: A qualitative study using semi-structured interviews was undertaken. Ethics approval was given by the University of Liverpool, and data were collected by IZ over 11 months from July 26, 2022, and May 26, 2023. Purposive sampling was used to recruit a general UK population sample (excluding health-care professionals) who were adults, partners, and parents, from an ethnic minority group, with recent diarrhoea, vomiting, or a stomach bug over the past 6 months. Recruitment was conducted through community gatekeepers using flyers. Participants were interviewed in person or virtually and gave written informed consent. An incentive of an Amazon voucher of £10 was imbursed to participants for their time. Interviews were audio-recorded using a password-protected digital recorder, transcribed verbatim, and analysed using reflexive thematic analysis. FINDINGS: 36 interviews (median age 31·5 years) were conducted with 11 women of Pakistani (n=6), Bangladeshi (n=2), Indian (n=2) and Arab ethnicity (n=1), and 25 men of Black (n=22), Pakistani (n=2), and Indian (n=1) ethnicity. This sample enabled an exploration of within-ethnic group experiences of stomach bugs in participants who self-defined their age, sex, and ethnicity. Themes such as managing food preparation (n=16), travel abroad (n=17), and personal cleanliness (n=3) were consistently reported across transcripts. The findings corroborate existing literature that there are more similarities than divergences in the management of stomach bugs across ethnic groups, such as the burden of care disproportionately affecting women and using over-the-counter medication to manage symptoms. INTERPRETATION: We do not know if the impact of these experiences across ethnic groups is entirely representative of the broader ethnic categories (ie, Asian vs Indian, Pakistani, and Bangladeshi) they belong to or if there are inequalities in their impact on ethnic groups living in different circumstances (ie, UK born vs migrant). FUNDING: National Institute for Health and Care Research (NIHR).

The role of toll-like receptors in immune tolerance induced by Helicobacter pylori infection.

Helicobacter pylori (H. pylori) is a gram-negative, microaerobic bacterium that colonizes the gastric mucosa in about half of the world's population. H. pylori infection can lead to various diseases. Chronic infection by H. pylori exposes the gastric mucosa to bacterial components such as lipopolysaccharide (LPS), outer membrane vesicles (OMVs), and several toxic proteins. Infected with H. pylori activates the release of pro-inflammatory factors and triggers inflammatory responses that damage the gastric mucosa. As the only microorganism that permanently colonizes the human stomach, H. pylori can suppress host immunity to achieve long-term colonization. Toll-like receptors (TLRs) play a crucial role in T-cell activation, promoting innate immune responses and immune tolerance during H. pylori infection. Among the 10 TLRs found in humans, TLR2, TLR4, TLR5, and TLR9 have been thoroughly investigated in relation to H. pylori-linked immune regulation. In the present review, we provide a comprehensive analysis of the various mechanisms employed by different TLRs in the induction of immune tolerance upon H. pylori infection, which will contribute to the research of pathogenic mechanism of H. pylori.