Helicobacters and cancer, not only gastric cancer?

The Helicobacter genus actually comprises 46 validly published species divided into two main clades: gastric and enterohepatic Helicobacters. These bacteria colonize alternative sites of the digestive system in animals and humans, and contribute to inflammation and cancers. In humans, Helicobacter infection is mainly related to H. pylori, a gastric pathogen infecting more than half of the world's population, leading to chronic inflammation of the gastric mucosa that can evolve into two types of gastric cancers: gastric adenocarcinomas and gastric MALT lymphoma. In addition, H. pylori but also non-H. pylori Helicobacter infection has been associated with many extra-gastric malignancies. This review focuses on H. pylori and its role in gastric cancers and extra-gastric diseases, as well as malignancies induced by non-H. pylori Helicobacters. Their different virulence factors and their involvement in carcinogenesis is discussed. This review highlights the importance of both gastric and enterohepatic Helicobacters in gastrointestinal and liver cancers.

Prevalence estimates of Helicobacter species infection in pancreatic and biliary tract cancers.

BACKGROUND: Helicobacter pylori infection is a well-established risk factor for gastric cancer and has been linked to other gastrointestinal diseases, including pancreatic and biliary tract cancers; however, the relevance of enterohepatic non-H. pylori helicobacters to the pathophysiology of these diseases remains unclear. MATERIALS AND METHODS: We estimated the prevalence of two enterohepatic non-H. pylori helicobacters (Helicobacter hepaticus and Helicobacter bilis) in the framework of a hospital-based case-control study involving 121 patients with biliary tract cancer, pancreatic cancer, or other gastrointestinal diseases. Bile and blood samples were collected from the patients undergoing endoscopic retrograde cholangiopancreatography. The presence of H. bilis, H. hepaticus, and other Helicobacter spp. was examined using bacterial culture, PCR-based detection, and serological tests. RESULTS: Culture of Helicobacter spp. from biliary brush samples was unsuccessful. Approximately 13.0% (15/115) of the bile samples collected from patients with a variety of gastrointestinal cancers, including pancreatic and biliary tract cancers, tested positive for one of the enterohepatic non-H. pylori helicobacter species as determined by PCR. Specifically, H. bilis and H. hepaticus DNA were detected in 11 and 4 bile samples, respectively. Approximately 20%-40% of the patients tested positive for serum non-H. pylori helicobacter IgG antibodies. The seroprevalence of H. bilis and H. hepaticus in the patients without evidence of H. pylori infection appeared to be higher in the pancreatic cancer group than in the control group. CONCLUSION: Our findings suggest a role for Helicobacter spp., especially H. bilis and H. hepaticus, in the etiology of pancreatic and biliary tract cancers.

Helicobacter species binding to the human gastric mucosa.

Helicobacter pylori infects half of the world population, being associated with several gastric disorders, such as chronic gastritis and gastric carcinoma. The Helicobacter genus also includes other gastric helicobacters, such as H. heilmannii¸ H. ailurogastricus, H. suis, H. felis, H. bizzozeronii, and H. salomonis. These gastric helicobacters colonize both the human and animal stomach. The prevalence of gastric non-Helicobacter pylori Helicobacter (NHPH) species in humans has been described as low, and the in vitro binding to the human gastric mucosa was never assessed. Herein, human gastric tissue sections were used for the evaluation of the tissue glycophenotype and for the binding of gastric NHPH strains belonging to different species. Histopathological evaluation showed that 37.5% of the patients enrolled in our cohort presented chronic gastritis, while the presence of neutrophil or eosinophilic activity (chronic active gastritis) was observed in 62.5% of the patients. The secretor phenotype was observed in 68.8% of the individuals, based on the expression of Lewis B antigen and binding of the UleX lectin. The in vitro binding assay showed that all the NHPH strains evaluated were able to bind, albeit in low frequency, to the human gastric mucosa. The H. heilmannii, H. bizzozeronii, and H. salomonis strains displayed the highest binding ability both to the gastric superficial epithelium and to the deep glands. Interestingly, we observed binding of NHPH to the gastric mucosa of individuals with severe chronic inflammation and intestinal metaplasia, suggesting that NHPH binding may not be restricted to the healthy gastric mucosa or slight chronic gastritis. Furthermore, the in vitro binding of NHPH strains was observed both in secretor and non-secretor individuals in a similar frequency. In conclusion, this study is the first report of the in vitro binding ability of gastric NHPH species to the human gastric mucosa. The results suggest that other glycans, besides the Lewis antigens, could be involved in the bacterial adhesion mechanism; however, the molecular intervenients remain unknown.

Presence of gastric Helicobacter species in children suffering from gastric disorders in Southern Turkey.

BACKGROUND: Infections with gastric Helicobacter spp. are associated with gastritis, peptic ulceration, and malignancies. Helicobacter pylori is the most prevalent Helicobacter species colonizing the human stomach. Other gastric non-H. pylori helicobacters (NHPHs) have been described in 0.2%-6% of human patients with gastric disorders. Nevertheless, due to difficulties in the diagnosis of NHPH infections and lack of routine screening, this is most likely an underestimation of their true prevalence. To the best of our knowledge, no studies have been performed in the presence of Helicobacter spp. in children suffering from gastric disorders in Southern Turkey. MATERIALS AND METHODS: In total, 110 children with gastric complaints were examined at the Cukurova University Balcali hospital, Turkey. Gastroscopy was performed to evaluate the presence of gastric mucosal lesions. Biopsies of the pyloric gland zone were taken for histopathological analysis, rapid urease testing, and presence of Helicobacter spp. DNA by PCR. RESULTS: Based on the PCR results, the prevalence of Helicobacter spp. was 32.7% (36/110). H. pylori was found in 30.9% (34/110), H. suis in 1.8% (2/110), and H. heilmannii/H. ailurogastricus in 0.9% (1/110) of the human patients. A mixed infection with H. pylori and H. suis was present in one patient. The presence of mucosal abnormalities, such as nodular inflammation, ulceration, and hyperemia, as well as gastritis, was significantly higher in Helicobacter spp. positive patients. CONCLUSION: Helicobacter pylori, H. suis, and H. heilmannii/H. ailurogastricus were present in children with gastric complaints. Infection with these pathogens may be involved in the development of gastritis and ulceration.

Other Helicobacters and the gastric microbiome.

The current article is a review of the most important, accessible, and relevant literature published between April 2017 and March 2018 on other Helicobacters and the gastric microbiome. The first part of the review focuses on literature describing non-Helicobacter pylori-Helicobacter (NHPH) infections in humans and animals whilst the subsequent section focuses specifically on the human gastric microbiome. Novel diagnostic methods as well as new NHPHs species have been identified in recent studies. Furthermore, our knowledge about the pathogenesis of NHPH infections has been further enhanced by important fundamental studies in cell lines and animal models. Over the last year, additional insights over the prevalence and potential prevention strategies of NHPHs have also been reported. With regard to understanding the gastric microbiome, new information detailing the structure of the gastric microbiota at different stages of H. pylori infection, within different patient geographical locations, was documented. There was also a study detailing the impact of proton-pump inhibitor usage and the effect on the gastric microbiome. Newer analysis approaches including defining the active microbiome through analysis of RNA rather than DNA-based sequencing were also published allowing the first assessments of the functional capabilities of the gastric microbiome.

Cholesterol-α-glucosyltransferase gene is present in most Helicobacter species including gastric non-Helicobacter pylori helicobacters obtained from Japanese patients.

BACKGROUND: Non-Helicobacter pylori helicobacters (NHPHs) besides H. pylori infect human stomachs and cause chronic gastritis and mucosa-associated lymphoid tissue lymphoma. Cholesteryl-α-glucosides have been identified as unique glycolipids present in H. pylori and some Helicobacter species. Cholesterol-α-glucosyltransferase (αCgT), a key enzyme for the biosynthesis of cholesteryl-α-glucosides, plays crucial roles in the pathogenicity of H. pylori. Therefore, it is important to examine αCgTs of NHPHs. MATERIALS AND METHODS: Six gastric NHPHs were isolated from Japanese patients and maintained in mouse stomachs. The αCgT genes were amplified by PCR and inverse PCR. We retrieved the αCgT genes of other Helicobacter species by BLAST searches in GenBank. RESULTS: αCgT genes were present in most Helicobacter species and in all Japanese isolates examined. However, we could find no candidate gene for αCgT in the whole genome of Helicobacter cinaedi and several enterohepatic species. Phylogenic analysis demonstrated that the αCgT genes of all Japanese isolates show high similarities to that of a zoonotic group of gastric NHPHs including Helicobacter suis, Helicobacter heilmannii, and Helicobacter ailurogastricus. Of 6 Japanese isolates, the αCgT genes of 4 isolates were identical to that of H. suis, and that of another 2 isolates were similar to that of H. heilmannii and H. ailurogastricus. CONCLUSIONS: All gastric NHPHs examined showed presence of αCgT genes, indicating that αCgT may be beneficial for these helicobacters to infect human and possibly animal stomachs. Our study indicated that NHPHs could be classified into 2 groups, NHPHs with αCgT genes and NHPHs without αCgT genes.

Cloning of Helicobacter suis cholesterol α-glucosyltransferase and production of an antibody capable of detecting it in formalin-fixed, paraffin-embedded gastric tissue sections.

Helicobacter suis (H. suis), formerly called Helicobacter heilmannii type 1 (H. heilmannii), is a gram-negative bacterium of the Helicobacter species. This pathogen infects the stomach of humans and animals such as dogs, cats, pigs, and rodents, the latter giving rise to zoonotic infection. Here, we generated a H. suis-specific antibody useful for immunohistochemistry with formalin-fixed, paraffin-embedded tissue sections. To do so, we began by cloning the gene encoding H. suis cholesterol α-glucosyltransferase (αCgT). αCgT is the key enzyme responsible for biosynthesis of cholesteryl α-D-glucopyranoside (CGL), a major cell wall component of Helicobacter species including H. suis. The deduced amino acid sequence of H. suis αCgT had 56% identity with the corresponding Helicobacter pylori (H. pylori). We then developed a polyclonal antibody (anti-Hh-I205R) by immunizing rabbits with a 205 amino acid H. suis αCgT fragment. Immunohistochemistry with the anti-Hh-I205R antibody could differentiate H. suis from H. pylori in gastric mucosa sections derived from mice infected with either pathogen. We then probed formalin-fixed, paraffin-embedded sections of human gastric mucosa positive for H. suis infection with the anti-Hh-I205R antibody and detected positive staining. These results indicate that anti-Hh-I205R antibody is specific for H. suis αCgT and useful to detect H. suis in gastric specimens routinely analyzed in pathological examinations.

Genome Dynamics and Molecular Infection Epidemiology of Multidrug-Resistant Helicobacter pullorum Isolates Obtained from Broiler and Free-Range Chickens in India.

Some life-threatening, foodborne, and zoonotic infections are transmitted through poultry birds. Inappropriate and indiscriminate use of antimicrobials in the livestock industry has led to an increased prevalence of multidrug-resistant bacteria with epidemic potential. Here, we present a functional molecular epidemiological analysis entailing the phenotypic and whole-genome sequence-based characterization of 11 H. pullorum isolates from broiler and free-range chickens sampled from retail wet markets in Hyderabad City, India. Antimicrobial susceptibility tests revealed all of the isolates to be resistant to multiple antibiotic classes such as fluoroquinolones, cephalosporins, sulfonamides, and macrolides. The isolates were also found to be extended-spectrum ß-lactamase producers and were even resistant to clavulanic acid. Whole-genome sequencing and comparative genomic analysis of these isolates revealed the presence of five or six well-characterized antimicrobial resistance genes, including those encoding a resistance-nodulation-division efflux pump(s). Phylogenetic analysis combined with pan-genome analysis revealed a remarkable degree of genetic diversity among the isolates from free-range chickens; in contrast, a high degree of genetic similarity was observed among broiler chicken isolates. Comparative genomic analysis of all publicly available H. pullorum genomes, including our isolates (n = 16), together with the genomes of 17 other Helicobacter species, revealed a high number (8,560) of H. pullorum-specific protein-encoding genes, with an average of 535 such genes per isolate. In silico virulence screening identified 182 important virulence genes and also revealed high strain-specific gene content in isolates from free-range chickens (average, 34) compared to broiler chicken isolates. A significant prevalence of prophages (ranging from 1 to 9) and a significant presence of genomic islands (0 to 4) were observed in free-range and broiler chicken isolates. Taken together, these observations provide significant baseline data for functional molecular infection epidemiology of nonpyloric Helicobacter species such as H. pullorum by unraveling their evolution in chickens and their possible zoonotic transmission to humans. IMPORTANCE: Globally, the poultry industry is expanding with an ever-growing consumer base for chicken meat. Given this, food-associated transmission of multidrug-resistant bacteria represents an important health care issue. Our study involves a critical baseline approach directed at genome sequence-based epidemiology and transmission dynamics of H. pullorum, a poultry pathogen having established zoonotic potential. We believe our studies would facilitate the development of surveillance systems that ensure the safety of food for humans and guide public health policies related to the use of antibiotics in animal feed in countries such as India. We sequenced 11 new genomes of H. pullorum as a part of this study. These genomes would provide much value in addition to the ongoing comparative genomic studies of helicobacters.

Other Helicobacters, gastric and gut microbiota.

The current article is a review of the most important and relevant literature published in 2016 and early 2017 on non-Helicobacter pylori Helicobacter infections in humans and animals, as well as interactions between H. pylori and the microbiota of the stomach and other organs. Some putative new Helicobacter species were identified in sea otters, wild boars, dogs, and mice. Many cases of Helicobacter fennelliae and Helicobacter cinaedi infection have been reported in humans, mostly in immunocompromised patients. Mouse models have been used frequently as a model to investigate human Helicobacter infection, although some studies have investigated the pathogenesis of Helicobacters in their natural host, as was the case for Helicobacter suis infection in pigs. Our understanding of both the gastric and gut microbiome has made progress and, in addition, interactions between H. pylori and the microbiome were demonstrated to go beyond the stomach. Some new approaches of preventing Helicobacter infection or its related pathologies were investigated and, in this respect, the probiotic properties of Saccharomyces, Lactobacillus and Bifidobacterium spp. were confirmed.

Genomic and clinical evidence uncovers the enterohepatic species Helicobacter valdiviensis as a potential human intestinal pathogen.

BACKGROUND: Helicobacter valdiviensis is a recently described enterohepatic species isolated from wild bird's fecal samples. Currently, its pathogenic potential and clinical significance are unknown mainly due to the lack of whole-genome sequences to compare with other helicobacters and the absence of specific screenings to determine its prevalence in humans. MATERIALS AND METHODS: The species type strain (WBE14T ) was whole-genome-sequenced, and comparative analyses were carried out including the genomes from other Helicobacter species to determine the exact phylogenetic position of H. valdiviensis and to study the presence and evolution of virulence determinants. In parallel, stools from diarrheic patients and healthy individuals were screened by PCR to assess the clinical incidence of H. valdiviensis. RESULTS: Helicobacter valdiviensis belongs to a monophyletic clade conformed by H. canadensis, H. pullorum, H. winghamensis, H. rodentium, and H. apodemus. Its predicted genome size is 2 176 246 bp., with 30% of G+C content and 2064 annotated protein-coding genes. The patterns of virulence factors in H. valdiviensis were similar to other enterohepatic species, but evidence of horizontal gene transfer from Campylobacter species was detected for key genes like those coding for the CDT subunits. Positive PCR results confirmed the presence of H. valdiviensis in 2 of 254 (0.78%) stools of patients with acute diarrhea while not a single sample was positive in healthy individuals. CONCLUSIONS: Horizontal gene transfer has contributed to shape the gene repertory of H. valdiviensis, which codes for virulence factors conserved in other pathogens that are well-known human pathogens. Additionally, the detection of H. valdiviensisDNA in diarrheic patients supports its role as a potential emergent intestinal pathogen. Further, sampling efforts are needed to uncover the clinical relevance of this species, which should be accomplished by the isolation of H. valdiviensis from ill humans and the obtention of whole genomes from clinical isolates.

A comparison of Helicobacter pylori and non-Helicobacter pylori Helicobacter spp. Binding to canine gastric mucosa with defined gastric glycophenotype.

BACKGROUND: The gastric mucosa of dogs is often colonized by non-Helicobacter pylori helicobacters (NHPH), while H. pylori is the predominant gastric Helicobacter species in humans. The colonization of the human gastric mucosa by H. pylori is highly dependent on the recognition of host glycan receptors. Our goal was to define the canine gastric mucosa glycophenotype and to evaluate the capacity of different gastric Helicobacter species to adhere to the canine gastric mucosa. MATERIALS AND METHODS: The glycosylation profile in body and antral compartments of the canine gastric mucosa, with focus on the expression of histo-blood group antigens was evaluated. The in vitro binding capacity of FITC-labeled H. pylori and NHPH to the canine gastric mucosa was assessed in cases representative of the canine glycosylation pattern. RESULTS: The canine gastric mucosa lacks expression of type 1 Lewis antigens and presents a broad expression of type 2 structures and A antigen, both in the surface and glandular epithelium. Regarding the canine antral mucosa, H. heilmannii s.s. presented the highest adhesion score whereas in the body region the SabA-positive H. pylori strain was the strain that adhered more. CONCLUSIONS: The canine gastric mucosa showed a glycosylation profile different from the human gastric mucosa suggesting that alternative glycan receptors may be involved in Helicobacter spp. binding. Helicobacter pylori and NHPH strains differ in their ability to adhere to canine gastric mucosa. Among the NHPH, H. heilmannii s.s. presented the highest adhesion capacity in agreement with its reported colonization of the canine stomach.

Use of Deep-Amplicon Sequencing (DAS), Real-Time PCR and In Situ Hybridization to Detect H. pylori and Other Pathogenic Helicobacter Species in Feces from Children.

BACKGROUND: Detecting Helicobacter pylori in fecal samples is easier and more comfortable than invasive techniques, especially in children. Thus, the objective of the present work was to detect H. pylori in feces from children by molecular methods as an alternative for diagnostic and epidemiological studies. METHODS: Forty-five fecal samples were taken from pediatric patients who presented symptoms compatible with H. pylori infection. HpSA test, culture, real-time quantitative PCR (qPCR), fluorescence in situ hybridization (FISH), direct viable count associated with FISH (DVC-FISH), and Illumina-based deep-amplicon sequencing (DAS) were applied. RESULTS: No H. pylori colonies were isolated from the samples. qPCR analysis detected H. pylori in the feces of 24.4% of the patients. In comparison, DVC-FISH analysis showed the presence of viable H. pylori cells in 53.3% of the samples, 37% of which carried 23S rRNA mutations that confer resistance to clarithromycin. After DAS, H. pylori-specific 16S rDNA sequences were detected in 26 samples. In addition, DNA from H. hepaticus was identified in 10 samples, and H. pullorum DNA was detected in one sample. CONCLUSION: The results of this study show the presence of H. pylori, H. hepaticus, and H. pullorum in children's stools, demonstrating the coexistence of more than one Helicobacter species in the same patient. The DVC-FISH method showed the presence of viable, potentially infective H. pylori cells in a high percentage of the children's stools. These results support the idea that fecal-oral transmission is probably a common route for H. pylori and suggest possible fecal-oral transmission of other pathogenic Helicobacter species.

Molecular Detection of Metronidazole and Tetracycline Resistance Genes in Helicobacter pylori-Like Positive Gastric Samples from Pigs.

Antimicrobial resistance is a major public health concern. The aim of this study was to assess the presence of antibiotic resistance genes, previously reported in Helicobacter pylori, in gastric samples of 36 pigs, in which DNA of H. pylori-like organisms had been detected. Based on PCR and sequencing analysis, two samples were positive for the 16S rRNA mutation gene, conferring tetracycline resistance, and one sample was positive for the frxA gene with a single nucleotide polymorphism, conferring metronidazole resistance. All three amplicons showed the highest homology with H. pylori-associated antibiotic resistance gene sequences. These findings indicate that acquired antimicrobial resistance may occur in H. pylori-like organisms associated with pigs.

Role of non-Helicobacter pylori gastric Helicobacters in helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma.

Marginal zone lymphomas rank as the third most prevalent form of non-Hodgkin B-cell lymphoma, trailing behind diffuse large B-cell lymphoma and follicular lymphoma. Gastric mucosa-associated lymphoid tissue lymphoma (GML) is a low-grade B-cell neoplasia frequently correlated with Helicobacter pylori (H. pylori)-induced chronic gastritis. On the other hand, a specific subset of individuals diagnosed with GML does not exhibit H. pylori infection. In contrast to its H. pylori-positive counterpart, it was previously believed that H. pylori-negative GML was less likely to respond to antimicrobial therapy. Despite this, surprisingly, in-creasing evidence supports that a considerable proportion of patients with H. pylori-negative GML show complete histopathological remission after bacterial eradication therapy. Nonetheless, the precise mechanisms underlying this treatment responsiveness are not yet fully comprehended. In recent years, there has been growing interest in investigating the role of non-H. pylori gastric helicobacters (NHPHs) in the pathogenesis of H. pylori-negative GML. However, additional research is required to establish the causal relationship between NHPHs and GML. In this minireview, we examined the current understanding and proposed prospects on the involvement of NHPHs in H. pylori-negative GML, as well as their potential response to bacterial eradication therapy.

Comprehensive Analysis of Gene Expression Profiling to Explore Predictive Markers for Eradication Therapy Efficacy against Helicobacter pylori-Negative Gastric MALT Lymphoma.

Although radiotherapy is the standard treatment for Helicobacter pylori (Hp)-negative gastric mucosa-associated lymphoid tissue (MALT) lymphoma, eradication therapy using antibiotics and an acid secretion suppressor can sometimes induce complete remission. We explored predictive markers for the response to eradication therapy for gastric MALT lymphoma that were negative for both API2-MALT1 and Hp infection using comprehensive RNA sequence analysis. Among 164 gastric MALT lymphoma patients who underwent eradication therapy as primary treatment, 36 were negative for both the API2-MALT1 fusion gene and Hp infection. Based on eradication therapy efficacy, two groups were established: complete response (CR) and no change (NC). The Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that cancer-related genes and infection-related genes were highly expressed in the NC and CR groups, respectively. Based on this finding and transcription factor, gene ontology enrichment, and protein-protein interaction analyses, we selected 16 candidate genes for predicting eradication therapy efficacy. Real-time PCR validation in 36 Hp-negative patients showed significantly higher expression of olfactomedin-4 (OLFM4) and the Nanog homeobox (NANOG) in the CR and NC groups, respectively. OLFM4 and NANOG could be positive and negative predictive markers, respectively, for eradication therapy efficacy against gastric MALT lymphoma that is negative for both API2-MALT1 and Hp infection.

Helicobacter trogontum Bacteremia and Lower Limb Skin Lesion in a Patient with X-Linked Agammaglobulinemia-A Case Report and Review of the Literature.

We describe the first case of infection with Helicobacter trogontum in a patient with X-linked agammaglobulinemia. A 22-year-old male with X-linked agammaglobulinemia presented with fever, malaise and a painful skin lesion on the lower left extremity. Spiral shaped Gram-negative rods were isolated from blood cultures and later identified as Helicobacter trogontum. The patient was treated with various intravenous and oral antibiotic regimens over a period of 10 months, each causing seemingly full clinical and paraclinical remission, yet several episodes of relapse occurred after cessation of antibiotic treatment. The review of the literature showed that only a few cases of infections with enterohepatic helicobacters belonging to the Flexispira rappini taxons have previously been reported. The majority of cases included patients with X-linked agammaglobulinemia and the symptomatology and course of disease were similar to the case described here. Infections with enterohepatic helicobacters, including Helicobacter trogontum, should be considered in patients with X-linked agammaglobulinemia presenting with fever, malaise and skin lesions. Careful cultivation and microbiological investigation are essential to determine the diagnosis and a long treatment period of over 6 months must be expected for successful eradication.

Helicobacter Species and Their Association with Gastric Pathology in a Cohort of Dogs with Chronic Gastrointestinal Signs.

Prevalence of individual Helicobacter species, data evaluating their association with gastric pathology and comparison of accuracy of diagnostic techniques are limited. The aims of this study were to determine the prevalence of gastric Helicobacter species, their association with gastric pathology, and to compare diagnostic techniques. Gastric biopsies from 84 privately-owned dogs with chronic gastrointestinal signs were obtained endoscopically. Helicobacters were detected using PCR, cytology, urease test, and histopathology. PCR detected helicobacters in 71.4% of dogs. Helicobacter heilmannii sensu stricto (s.s.) was the predominant species. Mixed infection was detected in 40% of PCR positive dogs. Gastritis was diagnosed in 38.5% of Helicobacter positive and 47.4% of Helicobacter negative dogs. Mono-infection was associated with 2.4 times increased odds of having more severe inflammation compared to mixed infection. Erosions and ulcers were common endoscopic lesions. Cytology had sensitivity/specificity of 88.3/91.7%. Association between infection and lymphoid follicular hyperplasia was demonstrated.

Helicobacter spp. in the Stomach of Cats: Successful Colonization and Absence of Relevant Histopathological Alterations Reveals High Adaptation to the Host Gastric Niche.

In addition to Helicobacter pylori, many non-Helicobacter pylori Helicobacters (NHPH) are able to cause gastric disease in humans. Cats are a natural reservoir for many of these species. Accordingly, living in close and intimate contact with animals has been identified as a risk factor, and an important zoonotic significance has therefore been attributed to NHPH. To determine the prevalence and associated gastric histopathological changes of Helicobacter species, the gastric mucosa of 71 cats were evaluated. Only four presented normal histopathological mucosa with the absence of spiral-shaped organisms. Normal gastric mucosa and the presence of spiral-shaped bacteria were observed in 13 cats. The remaining animals presented histopathological changes representative of gastritis. Helicobacter species were detected in 53 cats (74.6%) by at least one detection method. None of the animals were positive for H. pylori or for H. ailurogastricus. Helicobacter heilmannii organisms were identified in 20 animals, predominantly in the body gastric region. Helicobacter salomonis was the second most prevalent species (57.1%), although it was mainly found in association with other NHPH. Helicobacter felis and H. bizzozeronii were less frequently detected. The great majority of the Helicobacter spp. PCR-positive animals presented normal features regarding fibrosis/mucosal atrophy, neutrophils, eosinophils, or other inflammatory cells and lymphofollicular hyperplasia. Given the controversy and the strong evidence of absence of significant histopathological alterations associated with the presence of Helicobacter spp. in cats, it is possible to hypothesize that these bacteria may be able to adapt to the feline gastric microenvironment or even to comprise part of the gastric microbiome of this animal species. Thus, prudency must be taken when prescribing an antibiotic therapy based solely on the presence of these bacteria in the feline stomach.

Gastric mucosa-associated lymphoid tissue lymphoma in conjunction with multiple lymphomatous polyposis in the context of Helicobacter pylori and Helicobacter suis superinfection.

A 53-year-old woman visited a doctor and complained of chest discomfort after meals. Esophagogastroduodenoscopy showed multiple granular elevations in the gastric body. After biopsies from the elevations, she was diagnosed with mucosa-associated lymphoid tissue (MALT) lymphoma. Polymerase chain reaction also detected Helicobacter pylori and H. suis. Treatment to eradicate H. pylori and H. suis was successful. Endoscopic examination after the bacterial eradication treatment showed that multiple granular elevations remained in the gastric body; however, no lymphoma cells were found during histopathological examination. Thus, we reported a case of H. pylori-positive gastric MALT lymphoma with a unique morphology associated with H. suis superinfection.

Infections With Enterohepatic Non-H. pylori Helicobacter Species in X-Linked Agammaglobulinemia: Clinical Cases and Review of the Literature.

The genus Helicobacter is classified into two main groups according to its habitat: gastric and enterohepatic. Patients with X-linked agammaglobulinemia (XLA) appear to be associated with invasive infection with enterohepatic non-Helicobacter pylori species (NHPH), mainly H. cinaedi and H. bilis. Such infections are difficult to control and have a high potential for recurrence. The spectrum of illnesses caused by these species includes recurrent fever, bacteremia, arthritis, osteomyelitis, cellulitis, abdominal abscesses, and pyoderma gangrenosum-like ulcer. The presence of these Helicobacters is particularly difficult to diagnose and eradicate, as they are very fastidious bacteria and present resistance to several types of antibiotics. We report two clinical cases of XLA patients infected with H. bilis. These infections were chronic in these patients and could not be eradicated in one of them. We also review the cases of enterohepatic non-Helicobacter pylori species (NHPH) in patients with this inborn error of immunity.