The Importance of Toll‐like Receptors in NF‐κB Signaling Pathway Activation by Helicobacter pylori Infection and the Regulators of this Response

Helicobacter pylori (H. pylori) is a common pathogenic bacterium in the stomach that infects almost half of the population worldwide and is closely related to gastric diseases and some extragastric diseases, including iron‐deficiency anemia and idiopathic thrombocytopenic purpura. Both the Maastricht IV/Florence consensus report and the Kyoto global consensus report have proposed the eradication of H. pylori to prevent gastric cancer as H.pylori has been shown to be a major cause of gastric carcinogenesis. The interactions between H. pylori and host receptors induce the release of the proinflammatory cytokines by activating proinflammatory signaling pathways such as nuclear factor kappa B (NF‐κB), which plays a central role in inflammation, immune response, and carcinogenesis. Among these receptors, Toll‐like receptors (TLRs) are classical pattern recognition receptors in the recognition of H. pylori and the mediation of the host inflammatory and immune responses to H. pylori. TLR polymorphisms also contribute to the clinical consequences of H. pylori infection. In this review, we focus on the functions of TLRs in the NF‐κB signaling pathway activated by H. pylori, the regulators modulating this response, and the functions of TLR polymorphisms in H.pylori‐related diseases.     

Imbalance of Gastrointestinal Microbiota in the Pathogenesis of Helicobacter pylori‐Associated Diseases

The development of new nucleotide sequencing techniques and advanced bioinformatics tools has opened the field for studying the diversity and complexity of the gastrointestinal microbiome independent of traditional cultural methods. Owing largely to the gastric acid barrier, the human stomach was long thought to be sterile. The discovery of Helicobacter pylori, the gram‐negative bacterium that infects upwards of 50% of the global population, has started a major paradigm shift in our understanding of the stomach as an ecologic niche for bacteria. Recent sequencing analysis of gastric microbiota showed that H. pylori was not alone and the interaction of H. pylori with those microorganisms might play a part in H. pylori‐associated diseases such as gastric cancer. In this review, we summarize the available literature about the changes of gastrointestinal microbiota after H. pylori infection in humans and animal models, and discuss the possible underlying mechanisms including the alterations of the gastric environment, the secretion of hormones and the degree of inflammatory response. In general, information regarding the composition and function of gastrointestinal microbiome is still in its infancy, future studies are needed to elucidate whether and to what extent H. pylori infection perturbs the established microbiota. It is assumed that clarifying the role of gastrointestinal communities in H. pylori‐associated diseases will provide an opportunity for translational application as a biomarker for the risk of serious H. pylori diseases and perhaps identify specific organisms for therapeutic eradication.     

Helicobacter pylori recrudescence and its influencing factors

Helicobacter pylori (H pylori) is known as one of the most common infectious pathogens, with high infection and recurrence rates worldwide. The prevalence of H pylori is up to 90% in developing countries, while the annual recurrence rate is much higher than that in developed countries. Recurrence can occur either by recrudescence or reinfection. Compared with reinfection, the time window for recrudescence is generally shorter, followed by the recurrence of H pylori–associated diseases in the short‐term. Many factors are involved in the H pylori reinfection, such as the prevalence of H pylori infection, living conditions and economic development, health conditions and so forth. Previous studies focused less on H pylori recrudescence. Therefore, the influencing factors for H pylori recrudescence needed further exploration. This study reviewed the recrudescence of H pylori infection and its influencing factors.     

Review: Epidemiology of Helicobacter pylori infection

This review summarizes recent publications on the epidemiology of Helicobacter pylori. Two major systemic analyses, from Malaysia and Ethiopia, were published. The Brazilian Consensus Conference has stated that H pylori infection is an infectious disease with an indication for antimicrobial therapy. A continuous decrease in H pylori prevalence was reported from many regions worldwide, including Korea, China, Iran, and Austria. A cross‐sectional H pylori prevalence study conducted in the United Arab Emirates found 41% prevalence in a group of healthy children and adults. Several studies from Asia addressed H pylori prevalence in adults undergoing regular checkup. The largest of such studies, performed in Korea, involved 24 471 subjects and reported 41.5% seroprevalence. A relatively smaller study from East China on 3252 subjects reported 27.5% prevalence. In contrast, a study from Spain reported 87.2% seroprevalence. A report on the association between smoking and H pylori seropositivity was published on behalf of the Stomach Cancer Pooling (StoP) Project—a consortium of epidemiological studies of gastric cancer. Also, other potential risk factors, including occupational risk factors, water supply, and food were analyzed. Gastroesophageal reflux and sexual partners has been associated with a higher risk for H pylori acquisition, and gut microbiota was suggested to play a role in intrafamilial transmission of H pylori. Finally, in a few studies (from Mexico and Japan), the catalytic model for predicting the potential risk of acquiring H pylori infection in the future was used. As anticipated, a further decline in H pylori‐related disease was demonstrated by applying the modeling.     

Helicobacter Pylori infection of the gallbladder and the risk of chronic cholecystitis and cholelithiasis: A systematic review and meta‐analysis

Background

Helicobacter pylori is coexisted with various diseases, including chronic gastritis, ulcer, and gastric cancer. Besides, chronic cholecystitis and cholelithiasis are extremely widespread over the world, which are considered as high health‐care cost burdens of digestive diseases. Epidemiologic evidence on Helicobacter pylori infection in gallbladder increasing the risk of biliary diseases has been contradictory.

Aim

Conduct a meta‐analysis of overall studies and investigate an association between Helicobacter pylori infection of the gallbladder with chronic cholecystitis/cholelithiasis.

Methods

We used PubMed, EMBASE, and Cochrane library databases to identify all published studies before August 2017. Pooled odds ratios (OR) and corresponding 95% confidence intervals (CIs) were obtained using the random effects model. Heterogeneity, sensitivity, and stratified analyses were also performed.

Results

Eighteen studies involving 1544 participants and 1061 biliary cases with chronic cholecystitis/cholelithiasis were included. Helicobacter pylori infection of the gallbladder was significantly associated with an increased risk of chronic cholecystitis and cholecystitis (OR = 3.022; 95% CI, 1.897‐4.815; I² = 20.1%). In addition, country‐based subgroup analysis also showed a positive association between Helicobacter pylori positivity and chronic cholecystitis/cholelithiasis risk. The ORs (95% CIs) for Asian and non‐Asian region studies were 3.75 (1.83‐7.71) and 2.25 (1.29‐3.89), respectively.

Conclusion

This meta‐analysis suggests that infection of the gallbladder with Helicobacter pylori is closely related to an increased risk of chronic cholecystitis and cholelithiasis.     

Review: Impact of Helicobacter pylori on Alzheimer's disease: What do we know so far?

Background

Helicobacter pylori has changed radically gastroenterologic world, offering a new concept in patients' management. Over time, more medical data gave rise to diverse distant, extragastric manifestations and interactions of the “new” discovered bacterium. Special interest appeared within the field of neurodegenerative diseases and particularly Alzheimer's disease, as the latter and Helicobacter pylori infection are associated with a large public health burden and Alzheimer's disease ranks as the leading cause of disability. However, the relationship between Helicobacter pylori infection and Alzheimer's disease remains uncertain.

Methods

We performed a narrative review regarding a possible connection between Helicobacter pylori and Alzheimer's disease. All accessible relevant (pre)clinical studies written in English were included. Both affected pathologies were briefly analyzed, and relevant studies are discussed, trying to focus on the possible pathogenetic role of this bacterium in Alzheimer's disease.

Results

Data stemming from both epidemiologic studies and animal experiments seem to be rather encouraging, tending to confirm the hypothesis that Helicobacter pylori infection might influence the course of Alzheimer's disease pleiotropically. Possible main mechanisms may include the bacterium's access to the brain via the oral‐nasal‐olfactory pathway or by circulating monocytes (infected with Helicobacter pylori due to defective autophagy) through disrupted blood‐brain barrier, thereby possibly triggering neurodegeneration.

Conclusions

Current data suggest that Helicobacter pylori infection might influence the pathophysiology of Alzheimer's disease. However, further large‐scale randomized controlled trials are mandatory to clarify a possible favorable effect of Helicobacter pylori eradication on Alzheimer's disease pathophysiology, before the recommendation of short‐term and cost‐effective therapeutic regimens against Helicobacter pylori‐related Alzheimer's disease.     

Review: Epidemiology of Helicobacter pylori

This review summarizes the recent knowledge on the epidemiology of Helicobacter pylori and the potential modes of transmission. In addition to English language publications, the authors have included original full‐text publications from Russia and Latin America published in the original languages. High H pylori prevalence has been reported in Russia, Jordan, Iran, China, and Latin American countries as well as in Arctic populations in Canada. Indigenous inhabitants in the Arctic were found to be infected substantially more frequently than non‐indigenous inhabitants. In Amsterdam, the Netherlands, the ethnic minority groups were at a significantly higher risk of being H pylori seropositive compared to the Dutch population. For the first time, data on the prevalence from Armenia have been published indicating 41.5% H pylori prevalence. Convincing evidence on the decline of H pylori prevalence in Southeast Hungary and Taiwan was published. A study from Chile suggested high infection rates in newborns during the first month after birth. Two meta‐analyses covered the potential correlation between H pylori and periodontal diseases, therefore addressing the potential oro‐oral transmission rates. Periodontal disease was found to be more prevalent in H pylori‐infected subjects. Other studies addressed the potential role of drinking water and food products as well as socioeconomic factors in transmitting the infection. Several studies in Asia addressed annual reinfection rates of H pylori, ranging from 1.5% in China to 3.1% in Korea. Finally, a review was published on the current evidence and future perspective of analysing H pylori in ancient human remains by a metagenomic approach.     

Helicobacter pylori and Antibiotic Resistance,A Continuing and Intractable Problem

Helicobacter pylori, a human pathogen with a high global prevalence, is the causative pathogen for multiple gastrointestinal diseases, especially chronic gastritis, peptic ulcers, gastric mucosa‐associated lymphoid tissue lymphoma, and gastric malignancies. Antibiotic therapies remain the mainstay for H. pylori eradication; however, this strategy is hampered by the emergence and spread of H. pylori antibiotic resistance. Exploring the mechanistic basis of this resistance is becoming one of the major research questions in contemporary biomedical research, as such knowledge could be exploited to devise novel rational avenues for counteracting the existing resistance and devising strategies to avoid the development of a novel anti‐H. pylori medication. Encouragingly, important progress in this field has been made recently. Here, we attempt to review the current state and progress with respect to the molecular mechanism of antibiotic resistance for H. pylori. A picture is emerging in which mutations of various genes in H. pylori, resulting in decreased membrane permeability, altered oxidation–reduction potential, and a more efficient efflux pump system. The increased knowledge on these mechanisms produces hope that antibiotic resistance in H. pylori can ultimately be countered.     

Role of Probiotics in Pediatric Patients with Helicobacter pylori Infection: A Comprehensive Review of the Literature

Background: The current guidelines suggest the use of triple therapy as first choice treatment of Helicobacter pylori infection, although the eradication failure rate is more than 30%. Current interest in probiotics as therapeutic agents against H. pylori is stimulated not only by the clinical data showing efficacy of some probiotics in different gastrointestinal diseases but also by the increasing resistance of pathogenic bacteria to antibiotics, thus the interest for alternative therapies is a real actual topic. Aim: To review in vitro and in vivo studies on the role of probiotics in H. pylori infection focusing on the paediatric literature. Materials and methods: Pre‐clinical and clinical paediatric studies in English assessing the role of probiotics in H. pylori infection identified by MEDLINE search (1950–2009) were reviewed. Results: In vitro studies demonstrated an inhibitory activity of probiotics on H. pylori growth and that this effect is extremely strain specific. Available data in children indicate that probiotics seems to be efficacious for the prevention of antibiotic associated side‐effects, and might be of help for the prevention of H. pylori complications by decreasing H. pylori density and gastritis, and for the prevention of H. pylori colonization or re‐infection by inhibiting adhesion to gastric epithelial cells. There is no clear evidence that probiotics may increase the H. pylori eradication rate. Conclusion: Both in vitro and in vivo studies provide evidence that probiotics may represent a novel approach to the management of H. pylori infection.     

Review: Pathogenesis of Helicobacter pylori infection

The original strategies developed by Helicobacter pylori to persistently colonise its host and to deregulate its cellular functions make this bacterium an outstanding model to study host‐pathogen interaction and the mechanisms responsible for bacterial‐induced carcinogenesis. During the last year, significant results were obtained on the role of bacterial factors essential for gastric colonisation such as spiral shape maintenance, orientation through chemotaxis and the formation of bacteria clonal population islands inside the gastric glands. Particularities of the H pylori cell surface, a structure important for immune escape, were demonstrated. New insights in the bacterial stress response revealed the importance of DNA methylation‐mediated regulation. Further findings were reported on H pylori components that mediate natural transformation and mechanisms of bacterial DNA horizontal transfer which maintain a high level of H pylori genetic variability. Within‐host evolution was found to be niche‐specific and probably associated with physiological differences between the antral and oxyntic gastric mucosa. In addition, with the progress of CryoEM, high‐resolution structures of the major virulence factors, VacA and CagT4SS, were obtained. The use of gastric organoid models fostered research revealing, preferential accumulation of bacteria at the site of injury during infection. Several studies further characterised the role of CagA in the oncogenic properties of H pylori, identifying the activation of novel CagA‐dependent pathways, leading to the promotion of genetic instabilities, epithelial‐to‐mesenchymal transition and finally carcinogenesis. Recent studies also highlight that microRNA‐mediated regulation and epigenetic modifications, through DNA methylation, are key events in the H pylori‐induced tumorigenesis process.     

The association of garlic with Helicobacter pylori infection and gastric cancer risk: A systematic review and meta‐analysis

Background

Garlic may be protective against Helicobacter pylori infection and gastric cancer development. We conducted this study to quantitatively update evidence on garlic intake and gastric cancer with the inclusion of most recent cohort studies and qualitatively summarize epidemiological studies of garlic consumption and Helicobacter pylori infection.

Materials and Methods

PubMed, Embase, MEDLINE, and Cochrane Library were searched on April 2018. We conducted a meta‐analysis to determine whether garlic intake reduced gastric cancer risk using random‐effect models and a systematic review to summarize evidence on the association between garlic consumption and Helicobacter pylori infection. Risk of bias was assessed using tools of Cochrane risk of bias and Robins‐I for randomized and nonrandomized studies, respectively.

Results

Meta‐analysis of 18 studies (142 921 subjects) demonstrated high garlic consumption (as comparing the highest category to the lowest) was associated with a reduced gastric cancer risk (OR = 0.51, 95% CI = 0.44‐0.57). This association became nonsignificant if only derived from the prospective studies (OR = 0.95, 95% CI = 0.66‐1.24). Thirteen studies (4889 participants) were included in the systematic review for garlic consumption and Helicobacter pylori infection; ten of which found no significant results. The majority of these studies were poor in quality given the small sample size and high risk of bias.

Conclusions

Pooled evidence, mainly from case‐control studies, suggested a significant inverse association of garlic intake with gastric cancer risk. Given the limitations of included studies, current epidemiological evidence is not sufficient to reach any definite conclusion regarding the association of garlic with Helicobacter pylori infection.     

Superoxide dismutase from Helicobacter pylori suppresses the production of pro‐inflammatory cytokines during in vivo infection

Background

Helicobacter pylori has undergone considerable adaptation to allow chronic persistence within the gastric environment. While H. pylori‐associated diseases are driven by an excessive inflammation, severe gastritis is detrimental to colonization by this pathogen. Hence, H. pylori has developed strategies to minimize the severity of gastritis it triggers in its host. Superoxide dismutase (SOD) is well known for its role in protecting against oxidative attack; less recognized is its ability to inhibit immunity, shown for SOD from mammalian sources and those of some bacterial species. This study examined whether H. pylori SOD (HpSOD) has the ability to inhibit the host immune response to these bacteria.

Materials and Methods

The ability of recombinant HpSOD to modify the response to LPS was measured using mouse macrophages. A monoclonal antibody against HpSOD was generated and injected into H. pylori‐infected mice.

Results

Addition of HpSOD to cultures of mouse macrophages significantly inhibited the pro‐inflammatory cytokine response to LPS stimulation. A monoclonal antibody was generated that was specific for SOD from H. pylori. When injected into mice infected with H. pylori for 3 months, this antibody was readily detected in both sera and gastric tissues 5 days later. While treatment with anti‐HpSOD had no effect on H. pylori colonization at this time point, it significantly increased the levels of a range of pro‐inflammatory cytokines in the gastric tissues. This did not occur with antibodies against other antioxidant enzymes.

Conclusions

SOD from H. pylori can inhibit the production of pro‐inflammatory cytokine during in vivo infection.     

Impact of reactive oxygen species generation on Helicobacter pylori-related extragastric diseases: a hypothesis

Helicobacter pylori (H. pylori) induces reactive oxygen species (ROS) production that contribute to pathogenesis of a variety of H. pylori-related gastric diseases, as shown in animal and human studies. Helicobacter pylori infection is also associated with variety of systemic extragastric diseases in which H. pylori-related ROS production might also be involved in the pathogenesis of these systemic conditions. We proposed that Hp-related ROS may play a crucial role in the pathophysiology of Hp-related systemic diseases including Alzheimer’s disease, multiple sclerosis, glaucoma and other relative neurodegenerative diseases, thereby suggesting introduction of relative ROS scavengers as therapeutic strategies against these diseases which are among the leading causes of disability and are associated with a large public health global burden. Moreover, we postulated that H. pylori-related ROS might also be involved in the pathogenesis of extragastric common malignancies, thereby suggesting that H. pylori eradication might inhibit the development or delay the progression of aforementioned diseases. However, large-scale future studies are warranted to elucidate the proposed pathophysiological mechanisms, including H. pylori-related ROS, involved in H. pylori-associated systemic and malignant conditions.     

A lucid review of Helicobacter pylori‐induced DNA damage in gastric cancer

Helicobacter pylori (H pylori) is the main risk factor for gastric cancer (GC). In recent years, many studies have addressed the effects of H pylori itself and of H pylori‐induced chronic inflammation on DNA damage. Unrepaired or inappropriately repaired DNA damage is one possible carcinogenic mechanism. We may conclude that H pylori‐induced DNA damage is one of the carcinogenic mechanisms of GC. In this review, we summarize the interactions between H pylori and DNA damage and the effects of H pylori‐induced DNA damage on GC. Then, focusing on oxidative stress, we introduce the application of antioxidants in GC. At the end of this review, we discuss the outlook for further research on H pylori‐induced DNA damage.     

Impact factors that modulate gastric cancer risk in Helicobacter pylori‐infected rodent models

Gastric cancer causes a large social and economic burden to humans. Helicobacter pylori (H pylori) infection is a major risk factor for distal gastric cancer. Detailed elucidation of H pylori pathogenesis is significant for the prevention and treatment of gastric cancer. Animal models of H pylori‐induced gastric cancer have provided an invaluable resource to help elucidate the mechanisms of H pylori‐induced carcinogenesis as well as the interaction between host and the bacterium. Rodent models are commonly used to study H pylori infection because H pylori‐induced pathological processes in the stomachs of rodents are similar to those in the stomachs of humans. The risk of gastric cancer in H pylori‐infected animal models is greatly dependent on host factors, bacterial determinants, environmental factors, and microbiota. However, the related mechanisms and the effects of the interactions among these impact factors on gastric carcinogenesis remain unclear. In this review, we summarize the impact factors mediating gastric cancer risk when establishing H pylori‐infected animal models. Clarifying these factors and their potential interactions will provide insights to construct animal models of gastric cancer and investigate the in‐depth mechanisms of H pylori pathogenesis, which might contribute to the management of H pylori‐associated gastric diseases.     

Helicobacter pylori Infection – A Boon or a Bane: Lessons from Studies in a Low‐Prevalence Population

Helicobacter pylori (H. pylori) infection is etiologically associated with gastric cancer and peptic ulcer diseases which are both important public health burdens which could be largely eliminated by H. pylori eradication. However, some investigators urge caution based on the hypothesis that eradication of H. pylori may result in an increase in the incidence of gastroesophageal reflux disease, esophageal adenocarcinoma, and childhood asthma. The ethnic Malays of northeastern Peninsular Malaysia have long had a low prevalence of H. pylori infection and, as expected, the incidence of gastric cancer and its precursor lesions is exceptionally low. The availability of a population with a low H. pylori prevalence and generally poor sanitation allows separation of H. pylori from the hygiene hypothesis and direct testing of whether absence of H. pylori is associated with untoward consequence. Contrary to predictions, in Malays, erosive esophagitis, Barrett's esophagus, distal esophageal cancers, and childhood asthma are all of low incidence. This suggests that H. pylori is not protective rather the presence of H. pylori infection is likely a surrogate for poor hygiene and not an important source of antigens involved in the hygiene hypothesis. Helicobacter pylori in Malays is related to transmission from H. pylori‐infected non‐Malay immigrants. The factors responsible for low H. pylori acquisition, transmission, and burden of H. pylori infection in Malays remain unclear and likely involves a combination of environmental, host (gene polymorphisms), and strain virulence factors. Based on evidence from this population, absence of H. pylori infection is more likely to be boon than a bane.     

Iron trafficking system in Helicobacter pylori

Helicobacter pylori infections are closely associated with peptic ulcers, gastric malignancy and iron deficiency anemia. Iron is essential for almost all living organisms and the investigation of iron uptake and trafficking system is thus important to understand the pathological roles of H. pylori. Up to now, the iron trafficking system of H. pylori is not yet fully clear and merits further efforts in this regards. The available information about iron uptake and regulation has been discussed in this concise review, such as FeoB in ferrous transportation, FrpB2 in hemoglobin uptake, HugZ in heme processing, virulence factors (VacA and CagA) in transferrin utilization, Pfr and NapA in iron storage and Fur in iron regulation. The identified iron trafficking system will help us to understand the pathological roles of H. pylori in the various gastric diseases and iron deficiency anemia and stimulates further development of effective anti-bacterial drugs.     

Review: Pathogenesis of Helicobacter pylori infection

In this review, we shall focus on the last year progression understanding the pathogenesis of Helicobacter pylori infection in the light of recent data related to adaptation of H pylori to the harsh acidic environment in the stomach, colonization of gastric mucosa via interaction with mucin 5 (MUC5AC) and other host cell receptors, the ability to form biofilm, interference with the host metabolic pathways, and induction of neuroimmune cross‐talk as well as downregulation of gastric barrier homeostasis and its consequences for the disease development. The role of the membrane vesicles of these bacteria has been emphasized as an important source of virulence factors. Furthermore, we shall describe molecular and functional studies on new aspects of VacA and CagA virulence, including the role of urease in the upregulation of VacA toxicity, an epithelial‐mesenchymal transition mediated by CagA, and the role of interaction of HopQ adhesin with carcinoembryonic antigen‐related cell adhesion molecules (CEACAMs) in CagA translocation into the host cells by the type IV secretion system (T4SS). The role of molecular mimicry between a common sequence (ATVLA) of H pylori heat shock protein (Hsp) B and human Hsp60 in the induction of potentially autoreactive antibodies is discussed. All these new data illustrate further progress in understanding H pylori pathogenicity and facilitate the search for new therapeutic targets as well as development of immunoprophylaxis methods based on new chimeric UreB and HpA proteins.     

Seroprevalence of Helicobacter pylori in Korea: A multicenter,nationwide study conducted in 2015 and 2016

Background

The Korean College of Helicobacter and Upper Gastrointestinal Research has studied Helicobacter pylori (H. pylori) prevalence since 1998 and found a dynamic change in its prevalence in Korea. The aim of this study was to determine the recent H. pylori prevalence rate and compare it with that of previous studies according to socioeconomic variables.

Methods

We planned to enroll 4920 asymptomatic Korean adults from 21 centers according to the population distribution of seven geographic areas (Seoul, Gyeonggi, Gangwon, Chungcheong, Kyungsang, Cholla, and Jeju). We centrally collected serum and tested H. pylori serum IgG using a chemiluminescent enzyme immunoassay.

Results

We analyzed 4917 samples (4917/4920 = 99.9%) from January 2015 to December 2016. After excluding equivocal serologic results, the H. pylori seropositivity rate was 51.0% (2414/4734). We verified a decrease in H. pylori seroprevalence compared with previous studies performed in 1998, 2005, and 2011 (P < .0001). The H. pylori seroprevalence rate differed by area: Cholla (59.5%), Chungcheong (59.2%), Kyungsang (55.1%), Jeju (54.4%), Gangwon (49.1%), Seoul (47.4%), and Gyeonggi (44.6%). The rate was higher in those older than 40 years (38.1% in those aged 30‐39 years and 57.7% in those aged 40‐49 years) and was lower in city residents than in noncity residents at all ages.

Conclusions

Helicobacter pylori seroprevalence in Korea is decreasing and may vary according to population characteristics. This trend should be considered to inform H. pylori‐related policies.     

Lipopolysaccharide Structure and Biosynthesis in Helicobacter pylori

This review covers the current knowledge and gaps in Helicobacter pylori lipopolysaccharide (LPS) structure and biosynthesis. H. pylori is a Gram‐negative bacterium which colonizes the luminal surface of the human gastric epithelium. Both a constitutive alteration of the lipid A preventing TLR4 elicitation and host mimicry of the Lewis antigen decorated O‐antigen of H. pylori LPS promote immune escape and chronic infection. To date, the complete structure of H. pylori LPS is not available, and the proposed model is a linear arrangement composed of the inner core defined as the hexa‐saccharide (Kdo‐LD‐Hep‐LD‐Hep‐DD‐Hep‐Gal‐Glc), the outer core composed of a conserved trisaccharide (‐GlcNAc‐Fuc‐DD‐Hep‐) linked to the third heptose of the inner core, the glucan, the heptan and a variable O‐antigen, generally consisting of a poly‐LacNAc decorated with Lewis antigens. Although the glycosyltransferases (GTs) responsible for the biosynthesis of the H. pylori O‐antigen chains have been identified and characterized, there are many gaps in regard to the biosynthesis of the core LPS. These limitations warrant additional mutagenesis and structural studies to obtain the complete LPS structure and corresponding biosynthetic pathway of this important gastric bacterium.