Current Knowledge about Gastric Microbiota with Special Emphasis on Helicobacter pylori-Related Gastric Conditions.

The gastric milieu, because of its very low acidic pH, is very harsh for bacterial growth. The discovery of Helicobacter pylori (H.p.) has opened a new avenue for studies on the gastric microbiota, thus indicating that the stomach is not a sterile environment. Nowadays, new technologies of bacterial identification have demonstrated the existence of other microorganisms in the gastric habitat, which play an important role in health and disease. This bacterium possesses an arsenal of compounds which enable its survival but, at the same time, damage the gastric mucosa. Toxins, such as cytotoxin-associated gene A, vacuolar cytotoxin A, lipopolysaccharides, and adhesins, determine an inflammatory status of the gastric mucosa which may become chronic, ultimately leading to a gastric carcinoma. In the initial stage, H.p. persistence alters the gastric microbiota with a condition of dysbiosis, predisposing to inflammation. Probiotics and prebiotics exhibit beneficial effects on H.p. infection, and, among them, anti-inflammatory, antioxidant, and antibacterial activities are the major ones. Moreover, the association of probiotics with prebiotics (synbiotics) to conventional anti-H.p. therapy contributes to a more efficacious eradication of the bacterium. Also, polyphenols, largely present in the vegetal kingdom, have been demonstrated to alleviate H.p.-dependent pathologies, even including the inhibition of tumorigenesis. The gastric microbiota composition in health and disease is described. Then, cellular and molecular mechanisms of H.p.-mediated damage are clarified. Finally, the use of probiotics, prebiotics, and polyphenols in experimental models and in patients infected with H.p. is discussed.

Autoimmune Gastritis and Hypochlorhydria: Known Concepts from a New Perspective.

Autoimmune atrophic gastritis is an immune-mediated disease resulting in autoimmune destruction of the specialized acid-producing gastric parietal cells. As a consequence, in autoimmune atrophic gastritis, gastric acid secretion is irreversibly impaired, and the resulting hypochlorhydria leads to the main clinical manifestations and is linked, directly or indirectly, to the long-term neoplastic complications of this disease. In the last few years, autoimmune atrophic gastritis has gained growing interest leading to the acquisition of new knowledge on different aspects of this disorder. Although reliable serological biomarkers are available and gastrointestinal endoscopy techniques have substantially evolved, the diagnosis of autoimmune atrophic gastritis is still affected by a considerable delay and relies on histopathological assessment of gastric biopsies. One of the reasons for the diagnostic delay is that the clinical presentations of autoimmune atrophic gastritis giving rise to clinical suspicion are very different, ranging from hematological to neurological-psychiatric up to gastrointestinal and less commonly to gynecological-obstetric symptoms or signs. Therefore, patients with autoimmune atrophic gastritis often seek advice from physicians of other medical specialties than gastroenterologists, thus underlining the need for increased awareness of this disease in a broad medical and scientific community.

Microbiota and gastric cancer.

The discovery of Helicobacter pylori in 1982 drew to an end the stomach being considered as a sterile organ. Later, the progress in molecular methods, especially Next Generation Sequencing and metagenomics, has highlighted the fact that a diverse microbiota including five major phyla could also be present in the stomach. However, when present, H. pylori is the essential species and it influences the other bacterial communities in terms of richness and evenness. It is now well accepted that H. pylori is the main risk factor for gastric cancer, especially the strains harboring the cag pathogenicity island and the CagA oncoprotein, but the need for other factors from the host and the environment can explain the important difference between those infected and those developing gastric cancer. Several studies showed a difference between the gastric microbiota of patients at various stages of development of gastric premalignant and malignant lesions, showing globally a reduced microbial diversity and an increase in the presence of intestinal commensals, especially with nitrosative functions. Other studies showed an increase in oral microbiota. These data suggest that the gastric microbiota other than H. pylori may play a role in the last steps of gastric carcinogenesis. It must also be noted that in a limited number of cases, a virus: the Epstein Barr Virus is responsible for the evolution toward gastric cancer, while in others the mycobiota also needs to be explored. Finally, the use of mice models allowed an exploration of the role of different gastric microbiota in addition to H. pylori.

Prognostic effects of the gastric mucosal microbiota in gastric cancer.

Gastric cancer (GC) is one of the most common malignant tumors with a high incidence and mortality. Microbiota play a significant role in human health and disease. We aimed to investigate the prognostic value of the gastric microbiota in different stomach microhabitats. We used our previously published 16S rRNA gene sequence data. We retrospectively enrolled a cohort of 132 patients with GC with complete prognostic information and selected 78 normal tissues, 49 peritumoral tissues, and 112 tumoral tissues for microbiota analysis. Patients with different prognoses showed different gastric microbiota compositions and diversity. The association network of the abundant gastric microbiota was more complicated in patients with poor prognoses. In the peritumoral microhabitat of patients with good prognoses, Helicobacter was significantly increased, whereas Halomonas and Shewanella were significantly decreased relative to that in the peritumoral microhabitat of patients with poor prognoses. PiCRUSt analysis revealed that the peritumoral microbiota had more different Kyoto Encyclopedia of Genes and Genomes pathways than did the tumoral and normal microbiota. This study evaluated the long-term prognostic value of the gastric mucosal microbiota in patients with GC. These findings suggested that the characteristic alterations of the gastric mucosal microbiota may be markers for clinical outcomes in these patients.

Fecal Signatures of Streptococcus anginosus and Streptococcus constellatus for Noninvasive Screening and Early Warning of Gastric Cancer.

BACKGROUND & AIMS: Most patients with gastric cancer (GCa) are diagnosed at an advanced stage. We aimed to investigate novel fecal signatures for clinical application in early diagnosis of GCa. METHODS: This was an observational study that included 1043 patients from 10 hospitals in China. In the discovery cohort, 16S ribosomal RNA gene analysis was performed in paired samples (tissues and feces) from patients with GCa and chronic gastritis (ChG) to determine differential abundant microbes. Their relative abundances were detected using quantitative real-time polymerase chain reaction to test them as bacterial candidates in the training cohort. Their diagnostic efficacy was validated in the validation cohort. RESULTS: Significant enrichments of Streptococcus anginosus (Sa) and Streptococcus constellatus (Sc) in GCa tumor tissues (P < .05) and feces (P < .0001) were observed in patients with intraepithelial neoplasia, early and advanced GCa. Either the signature parallel test Sa∪Sc or single signature Sa/Sc demonstrated superior sensitivity (Sa: 75.6% vs 72.1%, P < .05; Sc: 84.4% vs 64.0%, P < .001; and Sa∪Sc: 91.1% vs 81.4%, P < .01) in detecting early GCa compared with advanced GCa (specificity: Sa: 84.0% vs 83.9%, Sc: 70.4% vs 82.3%, and Sa∪Sc: 64.0% vs 73.4%). Fecal signature Sa∪Sc outperformed Sa∪CEA/Sc∪CEA in the discrimination of advanced GCa (sensitivity: 81.4% vs 74.2% and 81.4% vs 72.3%, P < .01; specificity: 73.4% vs 81.0 % and 73.4% vs 81.0%). The performance of Sa∪Sc in the diagnosis of both early and advanced GCa was verified in the validation cohort. CONCLUSION: Fecal Sa and Sc are noninvasive, accurate, and sensitive signatures for early warning in GCa. (ClinicalTrials.gov, Number: NCT04638959).

Gastric microbiota in gastric cancer and precancerous stages: Mechanisms of carcinogenesis and clinical value.

Gastric cancer (GC) is a globally important disease. The discovery of Helicobacter pylori (H. pylori) demonstrated that the human stomach is not a sterile environment, and recent advances in molecular biology have led to the detection of large populations of microorganisms in the stomach. A growing number of studies have elucidated differences in the microbiota of patients at various stages of GC development. Evidence from insulin-gastrin transgenic (INS-GAS) and human gastric microbiota-transplanted mouse models have further demonstrated the potential causality of microbiota in the development of GC. To date, H. pylori is still thought to be the strongest risk factor for GC. H. pylori interacts with non-H. pylori commensals and affects the composition of the gastric microbiota. This review provides an overview of the relationship between the gastric microbiota and GC, including the mechanisms of microbe-associated carcinogenesis, the clinical value of the microbiota as a GC biomarker, and the potential of modulating the microbiota for GC prevention or therapy.

Microbiome and function alterations in the gastric mucosa of asymptomatic patients with Helicobacter pylori infection.

BACKGROUND: Most patients with Helicobacter pylori (H. pylori) infection have no clinical symptoms, numerous studies reported the gastric microbiome in H. pylori-infected patients, but asymptomatic patients have not been distinguished. How the microbiome and function changes in asymptomatic patients with H. pylori infection remains poorly understood. METHODS: A total of 29 patients were divided into H. pylori-infected asymptomatic group (10 patients), H. pylori-infected symptomatic group (11 patients) and H. pylori-uninfected group (8 patients). Gastric mucosa specimens were taken for histopathological examination, special staining, and 16 S rDNA sequencing. High-throughput results were evaluated by community composition analysis, indicator species analysis, alpha diversity analysis, beta diversity analysis, and function prediction. RESULTS: The gastric microbiota composition at phylum and genus level of H. pylori-infected asymptomatic patients were similar with H. pylori-infected symptomatic group, but different from H. pylori-uninfected patients. The diversity and richness of gastric microbial community declined significantly in H. pylori-infected asymptomatic group comparing with H. pylori-uninfected group. Sphingomonas may be an indicator between symptomatic and asymptomatic patients with H. pylori infection, the AUC value of Sphingomonas is 0.79. Interactions between species increased and altered notably after H. pylori infection. More genera were affected by Helicobacter in H. pylori-infected asymptomatic patients. The function condition changed significantly in asymptomatic patients with H. pylori infection, there was no difference comparing with symptomatic ones. Amino acid metabolism and lipid metabolism strengthened but carbohydrate metabolism remained constant after H. pylori infection. The metabolism of fatty acid and bile acid was disturbed after infection with H. pylori. CONCLUSION: The gastric microbiota composition and function mode changed significantly after H. pylori infection regardless of the presence of clinical symptoms, there was no difference between H. pylori-infected asymptomatic and symptomatic patients. The difference in gastric microbiota composition and interactions between species might be responsible for presence of digestive symptoms.

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

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

The relationship of gastric microbiota and Helicobacter pylori infection in pediatrics population.

BACKGROUND: In recent years, the impact of Helicobacter pylori (H pylori) on the gut microbiota has attracted more attention; however, the relationship in pediatric population rarely was reported. METHODS: Endoscopic gastric mucosal biopsy specimens from 55 children with gastrointestinal symptoms were collected, 37 of them were H pylori-positive (23 nonpeptic ulcer and 14 peptic ulcer) and 18 were H pylori-negative. In addition, 11 specimens were collected from H pylori-positive children who performed second endoscopy in 4 weeks after therapy. Microbial abundance and compositions were analyzed by 16S ribosomal RNA amplification and microbial functions were predicted using the software PICRUSt. RESULTS: The gastric microbiota of H pylori-positive children were mainly dominated by Helicobacter in genus (95.43%). The microbiota richness and diversity of H pylori-positive children were lower than that of H pylori-negative children. No difference was found in microbiota structure between H pylori-positive children with or without peptic ulcer. The richness and compositions after therapy were closer to the characteristics of H pylori-negative children. For predicted functions, higher abundance in pathways of infection diseases, cancer and lower abundance in the pathways of amino acid, lipid, and carbohydrate metabolism were found in H pylori-positive group than H pylori-negative group. CONCLUSION: The characteristics of gastric microbiota were affected by H pylori infection rather than disease states, and the richness and diversity of gastric species were inverse correlation with H pylori infection in children. Eradication therapy was helpful to restore shifted gastric microbiota.

Current Perspectives in Atrophic Gastritis.

PURPOSE OF THE REVIEW: Atrophic gastritis is a complex syndrome with gastric atrophy as a common trait. Helicobacter pylori infection and autoimmunity are the two main contexts in which it develops. It is slightly symptomatic, affects various aspects of general health, and remains a predisposing factor for gastric cancer. This review will update current knowledge and progress on atrophic gastritis. RECENT FINDINGS: Atrophic gastritis affects mostly adults with persistent dyspepsia, deficient anemia, autoimmunity disease, long-term proton pump inhibitor use, and a family history of gastric cancer. Gastric biopsies, expressed as Sydney system grade and OLGA/OLGIM classifications, represent the gold standard for diagnosis and cancer risk stage, respectively. Recently, electronic chromoendoscopy has allowed "targeted biopsies" of intestinal metaplasia. The associated hypochlorhydria affects the gastric microbiota composition suggesting that non-Helicobacter pylori microbiota may participate in the development of gastric cancer. Physicians should be aware of multifaceted clinical presentation of atrophic gastritis. It should be endoscopically monitored by targeted gastric biopsies. Autoimmune and Helicobacter pylori-induced atrophic gastritis are associated with different gastric microbial profiles playing different roles in gastric tumorigenesis.

Flavodoxins as Novel Therapeutic Targets against Helicobacter pylori and Other Gastric Pathogens.

Flavodoxins are small soluble electron transfer proteins widely present in bacteria and absent in vertebrates. Flavodoxins participate in different metabolic pathways and, in some bacteria, they have been shown to be essential proteins representing promising therapeutic targets to fight bacterial infections. Using purified flavodoxin and chemical libraries, leads can be identified that block flavodoxin function and act as bactericidal molecules, as it has been demonstrated for Helicobacter pylori (Hp), the most prevalent human gastric pathogen. Increasing antimicrobial resistance by this bacterium has led current therapies to lose effectiveness, so alternative treatments are urgently required. Here, we summarize, with a focus on flavodoxin, opportunities for pharmacological intervention offered by the potential protein targets described for this bacterium and provide information on other gastrointestinal pathogens and also on bacteria from the gut microbiota that contain flavodoxin. The process of discovery and development of novel antimicrobials specific for Hp flavodoxin that is being carried out in our group is explained, as it can be extrapolated to the discovery of inhibitors specific for other gastric pathogens. The high specificity for Hp of the antimicrobials developed may be of help to reduce damage to the gut microbiota and to slow down the development of resistant Hp mutants.

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.

The eradication of Helicobacter pylori restores rather than disturbs the gastrointestinal microbiota in asymptomatic young adults.

BACKGROUND: The eradication of Helicobacter pylori (H pylori) has been suggested to reduce the risk of gastric cancer, but its impact on the gut microbiota has attracted public attention. This study aimed to investigate the short-term and long-term effects of bismuth quadruple therapy on both gastric and fecal microbiota. METHODS: Ten asymptomatic young adults with H pylori-related gastritis were treated with bismuth quadruple therapy for 14 days, and 7 age-matched adults without H pylori infection were enrolled as healthy controls. Both fecal and gastric mucosa samples were collected from H pylori-positive patients at weeks 0, 6, and 26, while fecal samples were collected from healthy controls. The gastric and gut microbiota were analyzed by 16S rRNA gene sequencing. RESULTS: The structure of the gastric microbiota was significantly changed after the eradication of H pylori with increased alpha diversity over time. The relative abundance of H pylori sharply decreased from more than 70% to nearly 0% after treatment, while some beneficial bacteria, such as Lactobacillus and Bifidobacterium, were increased. The microbial diversity of gut microbiota was higher in H pylori-infected patients than in healthy controls, which tended to decrease after eradication. The potentially beneficial gut bacteria Blautia and Lachnoclostridium were enriched at week 26 compared to week 0, while the pathogenic Alistipes were depleted to a level close to that of the healthy controls. CONCLUSIONS: Bismuth quadruple therapy for H pylori eradication can restore the diversity of gastric microbiota with enrichment of beneficial bacteria. The composition of gut microbiota after H pylori eradication trends toward healthy status instead of becoming dysbiotic.

The relationship between gastric microbiota and gastric disease.

Traditionally, the stomach was believed to be a sterile organ unsuitable for microbiota growth. However, the discovery of H. pylori subverted this conception. With the development of molecular techniques, an abundance of microbiota of great diversity was found in the stomach. In addition, various lines of evidence suggest that the gastric microbiota plays a critical role in the development and progression of the gastric disease.The gastrointestinal microbiome plays an important role in various physiologic and pathologic processes.

Helicobacter pylori Infection, the Gastric Microbiome and Gastric Cancer.

After a long period during which the stomach was considered as an organ where microorganisms could not thrive, Helicobacter pylori was isolated in vitro from gastric biopsies, revolutionising the fields of Microbiology and Gastroenterology. Since then, and with the introduction of high-throughput sequencing technologies that allowed deep characterization of microbial communities, a growing body of knowledge has shown that the stomach contains a diverse microbial community, which is different from that of the oral cavity and of the intestine. Gastric cancer is a heterogeneous disease that is the end result of a cascade of events arising in a small fraction of patients colonized with H. pylori. In addition to H. pylori infection and to multiple host and environmental factors that influence disease development, alterations to the composition and function of the normal gastric microbiome, also known as dysbiosis, may also contribute to malignancy. Chronic inflammation of the mucosa in response to H. pylori may alter the gastric environment, paving the way to the growth of a dysbiotic gastric bacterial community. This dysbiotic microbiome may promote the development of gastric cancer by sustaining inflammation and/or inducing genotoxicity. This chapter summarizes what is known about the gastric microbiome in the context of H. pylori-associated gastric cancer, introducing the emerging dimension of the microbiome into the pathogenesis of this highly incident and deadly disease.

Impact of the Microbiota and Gastric Disease Development by Helicobacter pylori.

Microorganisms in humans form complex communities with important functions and differences in each part of the body. The stomach was considered to be a sterile organ until the discovery of Helicobacter pylori, but nowadays, it is possible to demonstrate that other microorganisms beyond H. pylori can colonize the gastric mucosa and that the diverse microbiota ecosystem of the stomach is different from the mouth and the esophagus, and also from the small intestine and large intestine. H. pylori seems to be the most important member of the gastric microbiota with the highest relative abundance when present, but when it is absent, the stomach has a diverse microbiota. Proteobacteria, Firmicutes, Actinobacteria, Bacteroidetes, and Fusobacteria are the most abundant phyla in both H. pylori-positive and H. pylori-negative patients. The gastric commensal flora may play some role in the H. pylori-associated carcinogenicity, and differences in the gastric microbiota composition of patients with gastric cancer, intestinal metaplasia, and chronic gastritis are described. The gastric microbiota changed gradually from non-atrophic gastritis to intestinal metaplasia, and to gastric cancer (type intestinal).

Gastric bacterial Flora in patients Harbouring Helicobacter pylori with or without chronic dyspepsia: analysis with matrix-assisted laser desorption ionization time-of-flight mass spectroscopy.

BACKGROUND: The gastric microbiota has recently been implicated in the causation of organic/structural gastroduodenal diseases (gastric and duodenal ulcers, gastric cancer) in patients with Helicobacter pylori (H. pylori) infection. We aimed to ascertain, in patients harbouring H. pylori, the role of the gastric microbiota in the causation of symptoms (chronic dyspepsia) in the absence of organic disease. METHODS: Seventy-four gastric biopsy samples obtained at endoscopy from patients with (n = 21) or without (n = 53) chronic dyspepsia, and that tested positive by the bedside rapid urease test for H. pylori infection, were cultured for detection of H. pylori and non-H. pylori organisms. The cultured organisms were identified by matrix-assisted laser desorption ionization time-of-flight mass spectroscopy (MALDI-TOF MS). RESULTS: A total of 106 non-H. pylori isolates were obtained from 74 patients' samples. This included 33 isolates (median 2, range 1-2 per patient) from dyspeptic and 73 (median 2, range 1-2 per patient) from non-dyspeptic patients. These were identified from the Bruker Biotyper 2 database as Staphylococcus spp., Streptococcus spp., Lactobacillus spp., Micrococcus spp., Enterococcus spp., Pseudomonas spp., Escherichia spp., Klebsiella spp. and Bacillus spp., Staphylococcus and Lactobacillus were identified significantly more commonly in dyspeptics and Streptococcus, Pseudomonas, Escherichia coli and Klebsiella pneumoniae in non-dyspeptics. All identified organisms belonged to the phyla Firmicutes and Proteobacteria. CONCLUSIONS: There is a qualitative difference in the gastric microbial spectrum between patients harbouring H. pylori with and without chronic dyspepsia. Whether these organisms have an independent role in the development or prevention of dyspepsia or act in concurrence with H. pylori needs study.

Is There a Role for the Non-Helicobacter pylori Bacteria in the Risk of Developing Gastric Cancer?

Helicobacter pylori is the most abundant bacterium in the gastric epithelium, and its presence has been associated with the risk of developing gastric cancer. As of 15 years ago, no other bacteria were associated with gastric epithelial colonization; but thanks to new methodologies, many other non-H. pylori bacteria have been identified. It is possible that non-H. pylori may have a significant role in the development of gastric cancer. Here, we discuss the specific role of H. pylori as a potential trigger for events that may be conducive to gastric cancer, and consider whether or not the rest of the gastric microbiota represent an additional risk in the development of this disease.

Helicobacter pylori infection in children.

Helicobacter pylori infection in children differs from that in adults, from the point of view of epidemiology, host response, clinical features, related diseases, and diagnosis, as well as treatment strategies. The prevalence of H. pylori infection, in both children and adults, is decreasing in the Western World as well as in some developing countries, which contrasts with the increase in childhood asthma and allergic diseases. Recurrent abdominal pain is not specific during H. pylori infection in children. The role of H. pylori infection and failure to thrive, children's growth, type I diabetes mellitus (T1DM) and celiac disease remains controversial. The main initial diagnosis is based on upper digestive endoscopy with biopsy-based methods. Nodular gastritis may be a pathognomonic endoscopic finding of childhood H. pylori infection. The infection eradication control is based on validated noninvasive tests. The main cause of treatment failure of H. pylori infection is its clarithromycin resistance. We recommend standard antibiotic susceptibility testing of H. pylori in pediatric patients prior to the initiation of eradication therapy. H. pylori treatment in children should be based on an evaluation of the rate of eradication in the local population, a systematic use of a treatment adapted to the susceptibility profile and a treatment compliance greater than 90%. The last meta-analysis in children did not show an advantage for sequential therapy when compared to a 14-day triple therapy. Finally, the high rate of antibiotic resistance responsible for therapy failure in recent years justifies the necessity of a novel vaccine to prevent H. pylori infection in children.

Other Helicobacters and gastric microbiota.

This article aimed to review the literature from 2015 dealing with gastric and enterohepatic non-Helicobacter pylori Helicobacter species (NHPH). A summary of the gastric microbiota interactions with H. pylori is also presented. An extensive number of studies were published during the last year and have led to a better understanding of the pathogenesis of infections with NHPH. These infections are increasingly reported in human patients, including infections with H. cinaedi, mainly characterized by severe bacteremia. Whole-genome sequencing appears to be the most reliable technique for identification of NHPH at species level. Presence of NHPH in laboratory animals may influence the outcome of experiments, making screening and eradication desirable. Vaccination based on UreB proteins or bacterial lysate with CCR4 antagonists as well as oral glutathione supplementation may be promising strategies to dampen the pathogenic effects associated with gastric NHPH infections. Several virulent factors such as outer membrane proteins, phospholipase C-gamma 2, Bak protein, and nickel-binding proteins are associated with colonization of the gastric mucosae and development of gastritis. The development of high-throughput sequencing has led to new insights in the gastric microbiota composition and its interaction with H. pylori. Alterations in the gastric microbiota caused by the pH-increasing effect of a H. pylori infection may increase the risk for gastric cancer.