The role of Helicobacter suis, Fusobacterium gastrosuis, and the pars oesophageal microbiota in gastric ulceration in slaughter pigs receiving meal or pelleted feed.

This study investigated the role of causative infectious agents in ulceration of the non-glandular part of the porcine stomach (pars oesophagea). In total, 150 stomachs from slaughter pigs were included, 75 from pigs that received a meal feed, 75 from pigs that received an equivalent pelleted feed with a smaller particle size. The pars oesophagea was macroscopically examined after slaughter. (q)PCR assays for H. suis, F. gastrosuis and H. pylori-like organisms were performed, as well as 16S rRNA sequencing for pars oesophagea microbiome analyses. All 150 pig stomachs showed lesions. F. gastrosuis was detected in 115 cases (77%) and H. suis in 117 cases (78%), with 92 cases (61%) of co-infection; H. pylori-like organisms were detected in one case. Higher infectious loads of H. suis increased the odds of severe gastric lesions (OR = 1.14, p = 0.038), while the presence of H. suis infection in the pyloric gland zone increased the probability of pars oesophageal erosions [16.4% (95% CI 0.6-32.2%)]. The causal effect of H. suis was mediated by decreased pars oesophageal microbiome diversity [-1.9% (95% CI - 5.0-1.2%)], increased abundances of Veillonella and Campylobacter spp., and decreased abundances of Lactobacillus, Escherichia-Shigella, and Enterobacteriaceae spp. Higher infectious loads of F. gastrosuis in the pars oesophagea decreased the odds of severe gastric lesions (OR = 0.8, p = 0.0014). Feed pelleting had no significant impact on the prevalence of severe gastric lesions (OR = 1.72, p = 0.28). H. suis infections are a risk factor for ulceration of the porcine pars oesophagea, probably mediated through alterations in pars oesophageal microbiome diversity and composition.

Incidences of Helicobacter infection in pigs and tracing occupational hazard in pig farmers.

Helicobacter species (spp.) is a gram-negative spiral-shaped motile bacterium that causes gastritis in pigs and also colonizes in the human stomach. The present study assessed the prevalence of Helicobacter spp. in pig gastric mucosa and the stool of pig farmers in Assam, India. A total of 403 stomach samples from pig slaughter points, 74 necropsy samples of pigs from pig farms, and 97 stool samples from pig farmers were collected. Among the pig stomach samples, 43 (20.09%) of those with gastritis showed the presence of Gram-negative, spiral-shaped organisms, while only 3.04% of stomach samples without lesions had these organisms. Scanning Electron Microscopy (SEM) of urease-positive stomach samples revealed tightly coiled Helicobacter bacteria in the mucus lining. Histopathological examination showed chronic gastritis with hemorrhagic necrosis, leucocytic infiltration, and lymphoid aggregates. PCR confirmed the presence of Helicobacter suis in 19.63% of pig stomach samples and 2.08% of pig farmer stool samples. Additionally, 3.12% of the stool samples from pig farmers were positive for Helicobacter pylori. Phylogenetic analysis revealed distinct clusters of Helicobacter suis with other Helicobacter spp. These findings highlight the prevalence of Helicobacter in both pig gastric mucosa and pig farmer stool. The findings highlight the need for improved sanitation and hygiene practices among pig farmers to minimize the risk of Helicobacter infection in humans.

Clinical presentation and outcomes of Helicobacter heilmannii gastritis in children in the New England region of the United States.

OBJECTIVE: To describe the clinical, endoscopic, histologic, and treatment outcomes of Helicobacter heilmannii (H. heilmannii) associated gastritis in children in the New England region of the United States. METHODS: Retrospective study of children (1-18 years) with H. heilmannii identified on gastric mucosal biopsies from two pediatric centers over a 21-year period, January 2000-December 2021. Cases were identified by querying pathology databases at each institution. Demographic and clinical data were obtained from the medical record. Endoscopic and histologic findings were extracted from endoscopy and pathology reports, respectively. RESULTS: Thirty-eight children were diagnosed with H. heilmannii-associated gastritis during the study period. The mean age at diagnosis was 10.1 ± 5.3 years, and 25/38 (66%) cases were male. Abdominal pain (32%) and nausea with or without vomiting (26%) were the most common symptoms. Thirty-two children (84%) had endoscopic findings including gastric nodularity (55%) and erythema (26%). All children had histologic signs of chronic gastritis, including those with normal endoscopic exams. Antibiotic regimens used for treating Helicobacter pylori were frequently prescribed. Of the 17 children who underwent a follow-up endoscopy (range 2-68 months), 15 (88%) did not have H. heilmannii identified on gastric biopsies. CONCLUSION: H. heilmannii was an infrequent but potential cause of epigastric abdominal pain and nausea in our cohort of New England children. While morphologically distinct from H. pylori, the bacteria can result in similar endoscopic and histologic findings of nodularity and chronic gastritis, respectively. The rate of eradication, as assessed by histology following treatment with H. pylori therapies, was below the 90% recommended goal for antimicrobial therapies.

Helicobacter ailurogastricus in Patient with Multiple Refractory Gastric Ulcers, Japan.

We report the isolation of Helicobacter ailurogastricus, a Helicobacter species that infects cats and dogs, from a person with multiple refractory gastric ulcers. In addition to H. suis, which infects pigs, Helicobacter species that infect cats and dogs should be considered as potential gastric pathogens in humans.

Perception and Knowledge of Portuguese Veterinarians about the Zoonotic Transmission of Helicobacter pylori and Helicobacter suis: The Need for One Health Intervention.

Helicobacter species can colonize the gastrointestinal tract of both humans and animals, and are associated with gastrointestinal and extra-gastrointestinal diseases. Some studies indicate that animals, health professionals, and people in close contact with animals might be at higher risk for infection with gastric Helicobacter spp. Considering that veterinarians are professionals at risk for infection with zoonotic gastric Helicobacters and are also seen by many as health communicators concerning zoonoses, the aim of this study was to evaluate the Portuguese veterinarians' perception and knowledge of Helicobacter spp. infection and its zoonotic risk/potential. Therefore, a structured questionnaire composed of 34 dichotomic, multiple-choice, rating scale, matrix, drop-down, and open-ended questions was developed and given to Portuguese veterinarians via an online platform from May 2021 to July 2021, and statistical analysis was used to obtain results. There was a total of 149 respondents, most of them (73.8%) being females. Evidently, Portuguese veterinarians have a limited perception regarding Helicobacter spp. infections. Of the respondents that "have heard of Helicobacter", 17.6% do not know which animal species can be affected by it. Most of the companion animal veterinarians (76.2%) do not consider Helicobacter spp. infection a differential diagnosis when evaluating animals with gastritis. A significant percentage (37.2%) of the respondents that have "heard of H. suis" do not consider it a zoonotic bacterium. There is a need for education and sensitization of veterinarians regarding the potential zoonotic risk of Helicobacter spp. in order to elucidate these professionals to this One Health issue, as the number of reports of non-Helicobacter pylori Helicobacter in livestock, companion, and wild animals is increasing.

Elevated carbohydrate antigen 19-9 following Helicobacter suis gastritis and normalisation after eradication: first case report and review of the literature.

Carbohydrate antigen 19-9 (CA 19-9) is a biological marker used to diagnose and monitor the progression of various cancers. Elevated CA 19-9 has also been sporadically observed in Helicobacter pylori infected patients. Similar to H. pylori, animalhosted non-H. pylori Helicobacter (NHPH) species can induce gastroduodenal lesions in humans. We report the first case of CA 19-9 elevation related to H. suis gastritis and its normalisation after eradication. A CA 19-9 screening prescribed as part of a regular check up by the general practitioner was found elevated in a 68-year-old man presenting chronic dyspeptic symptoms. Medical investigations were negative for presence of neoplasia or biliary obstruction. Upper gastrointestinal endoscopy confirmed the presence of chronic gastritis and H. suis was identified in gastric biopsies. The standard treatment for H. pylori successfully eradicated H. suis with normalisation of CA 19-9 levels. In addition to H. pylori, infection with NHPH species should be considered as an additional cause of elevated CA19-9.

Gastric Helicobacter species associated with dogs, cats and pigs: significance for public and animal health.

This article focuses on the pathogenic significance of Helicobacter species naturally colonizing the stomach of dogs, cats and pigs. These gastric "non-Helicobacter (H.) pylori Helicobacter species" (NHPH) are less well-known than the human adapted H. pylori. Helicobacter suis has been associated with gastritis and decreased daily weight gain in pigs. Several studies also attribute a role to this pathogen in the development of hyperkeratosis and ulceration of the non-glandular stratified squamous epithelium of the pars oesophagea of the porcine stomach. The stomach of dogs and cats can be colonized by several Helicobacter species but their pathogenic significance for these animals is probably low. Helicobacter suis as well as several canine and feline gastric Helicobacter species may also infect humans, resulting in gastritis, peptic and duodenal ulcers, and low-grade mucosa-associated lymphoid tissue lymphoma. These agents may be transmitted to humans most likely through direct or indirect contact with dogs, cats and pigs. Additional possible transmission routes include consumption of water and, for H. suis, also consumption of contaminated pork. It has been described that standard H. pylori eradication therapy is usually also effective to eradicate the NHPH in human patients, although acquired antimicrobial resistance may occasionally occur and porcine H. suis strains are intrinsically less susceptible to aminopenicillins than non-human primate H. suis strains and other gastric Helicobacter species. Virulence factors of H. suis and the canine and feline gastric Helicobacter species include urease activity, motility, chemotaxis, adhesins and gamma-glutamyl transpeptidase. These NHPH, however, lack orthologs of cytotoxin-associated gene pathogenicity island and vacuolating cytotoxin A, which are major virulence factors in H. pylori. It can be concluded that besides H. pylori, gastric Helicobacter species associated with dogs, cats and pigs are also clinically relevant in humans. Although recent research has provided better insights regarding pathogenic mechanisms and treatment strategies, a lot remains to be investigated, including true prevalence rates, exact modes of transmission and molecular pathways underlying disease development and progression.

Clinical aspects of Helicobacter heilmannii-associated gastritis in patients with dyspepsia: A systematic review and meta-analysis.

BACKGROUND: The clinical relevance of Helicobacter heilmannii (H. heilmannii) infection in patients with upper gastrointestinal diseases is not yet fully understood. The main purpose of this study was to evaluate the clinical, endoscopic, histopathological, and therapeutic features of H. heilmannii. METHODS: To retrieve the relevant studies, we conducted a comprehensive systematic search of global databases such as the ISI Web of Science, PubMed, Scopus, Embase, and Google Scholar. After confirming the studies based on the inclusion criteria statistical analysis was performed using Comprehensive Meta-Analysis software. RESULTS: In our study, the prevalence of infection with H. heilmannii was measured at 1.9% (95% CI: 0.8-4.2). The prevalence of H. heilmannii in Asian population was higher than Western countries (3.1% vs. 1.2%, respectively). Interestingly, the frequency of coinfection with both H. pylori and H. heilmannii was 15.4% (95% CI: 5.2-37.6). The most common endoscopic findings were chronic gastritis, hyperplasia, and erosion. In addition, our results showed that in people infected with this bacterium, gastric inflammation is typically chronic, focal, and less active than Helicobacter pylori (H. pylori) gastritis. Conventional treatment of H. pylori can lead to the eradication of H. heilmannii. CONCLUSION: In general, H. heilmannii infection is significantly associated with mild chronic gastritis and can be treated with standard anti-H. pylori treatment.

Investigation of endoscopic findings in nine cases of Helicobacter suis-infected gastritis complicated by gastric mucosa-associated lymphoid tissue lymphoma.

BACKGROUND: We have previously reported that eradication therapy was more effective against Helicobacter pylori (Hp)-negative gastric mucosa-associated lymphoid tissue (MALT) lymphoma in non-Helicobacter pylori Helicobacter (NHPH)-positive cases than in NHPH-negative cases and that the infection status of NHPH could be a predictive marker for the efficacy of eradication therapy for H. pylori negative gastric MALT lymphoma. However, a diagnostic test for NHPH infection has not yet been clinically established. In this study, we investigated the endoscopic findings in cases of H. suis-infected gastritis associated with gastric MALT lymphoma reported at our institution. MATERIALS AND METHODS: Participants were selected from cases of gastric MALT lymphoma who underwent esophagogastroduodenoscopy at Hiroshima University Hospital, who were negative for the API2-MALT1 gene, and who received eradication therapy as a first-line treatment. We examined the endoscopic findings in nine cases from this group in which H. suis infection was confirmed by polymerase chain reaction. RESULTS: Endoscopic findings, such as cracked mucosa, spotty redness, nodular gastritis-like appearance, and white marbled appearance, which have been reported as characteristics of NHPH gastritis, were observed in multiple cases. The most common endoscopic findings in this study were cracked mucosa (7/9 cases), followed by spotty redness (6/9 cases), nodular gastritis-like appearance (5/9 cases), and white marbled appearance (2/9 cases). CONCLUSIONS: Our study may serve as a reference for re-evaluation of the diagnostic criteria for H. suis infection and indications for eradication therapy, particularly for cases of H. pylori negative gastric MALT lymphoma, where endoscopic findings such as those seen in this study were observed in the background mucosa.

An exploratory study on the presence of Helicobacter heilmannii and Helicobacter billis in the feces of companion dogs.

BACKGROUND: Companion animals like dogs play an important role in the lives of many people and are often considered to be members of families, but definitely, any contact with them poses an inherent risk of transmitting zoonotic pathogens. One of these pathogens is the genus Helicobacter which is linked to many disorders in human and animal. OBJECTIVES: The aim of this study was to investigate the presence of some zoonotic species of genus Helicobacter in companion dogs. RESULTS: Through culturing in a special medium, nine samples (9%) were detected as infected (two pure and seven mixed culture). Based on multiplex-PCR, 13 samples (13%) were infected by Helicobacter spp. although none of them were infected by H. pylori. Species-specific PCR indicated that 38.5% or 5/13 of the samples were infected with H. heilmannii, while 15.45% or 2/13 of the samples were infected by H. billis. Multivariate logistic regression analysis showed that the age factor had a significant effect on Helicobacter spp. infection (odds ratio [OR] = 2.42, p = 0.01). CONCLUSION: This study revealed the negligible faecal transmission of H. pylori. Moreover, due to the detection of H. Heilmannii and H. billis in feces and their association with human gastric diseases, dog owners should be educated about the risks and transmission modes of zoonotic bacterial infections of dogs.

Protocol for generating a mouse model of gastric MALT lymphoma and the identification of MALT lymphoma cell populations by immunostaining.

Helicobacter suis, a zoonotic infection-related bacterium, induces gastric mucosa-associated lymphoid tissue (MALT) lymphoma in humans and animals. However, a lack of suitable animal models complicates the detailed analysis of this disease. Here, we describe the generation of a gastric MALT lymphoma mouse model. We then detail the use of this model combined with an immunostaining protocol to identify the cell populations that constitute gastric MALT lymphoma. This protocol can be used to identify the constituent cells of human MALT lymphoma. For complete details on the use and execution of this profile, please refer to Yamamoto et al. (2021).

Gastric Helicobacter suis Infection Partially Protects against Neurotoxicity in A 6-OHDA Parkinson's Disease Mouse Model.

The exact etiology of Parkinson's disease (PD) remains largely unknown, but more and more research suggests the involvement of the gut microbiota. Interestingly, idiopathic PD patients were shown to have at least a 10 times higher prevalence of Helicobacter suis (H. suis) DNA in gastric biopsies compared to control patients. H. suis is a zoonotic Helicobacter species that naturally colonizes the stomach of pigs and non-human primates but can be transmitted to humans. Here, we investigated the influence of a gastric H. suis infection on PD disease progression through a 6-hydroxydopamine (6-OHDA) mouse model. Therefore, mice with either a short- or long-term H. suis infection were stereotactically injected with 6-OHDA in the left striatum and sampled one week later. Remarkably, a reduced loss of dopaminergic neurons was seen in the H. suis/6-OHDA groups compared to the control/6-OHDA groups. Correspondingly, motor function of the H. suis-infected 6-OHDA mice was superior to that in the non-infected 6-OHDA mice. Interestingly, we also observed higher expression levels of antioxidant genes in brain tissue from H. suis-infected 6-OHDA mice, as a potential explanation for the reduced 6-OHDA-induced cell loss. Our data support an unexpected neuroprotective effect of gastric H. suis on PD pathology, mediated through changes in oxidative stress.

Isolation and characterization of Helicobacter suis from human stomach.

Helicobacter suis, a bacterial species naturally hosted by pigs, can colonize the human stomach in the context of gastric diseases such as gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Because H. suis has been successfully isolated from pigs, but not from humans, evidence linking human H. suis infection to gastric diseases has remained incomplete. In this study, we successfully in vitro cultured H. suis directly from human stomachs. Unlike Helicobacter pylori, the viability of H. suis decreases significantly on neutral pH; therefore, we achieved this using a low-pH medium for transport of gastric biopsies. Ultimately, we isolated H. suis from three patients with gastric diseases, including gastric MALT lymphoma. Successful eradication of H. suis yielded significant improvements in endoscopic and histopathological findings. Oral infection of mice with H. suis clinical isolates elicited gastric and systemic inflammatory responses; in addition, progression of gastric mucosal metaplasia was observed 4 mo postinfection. Because H. suis could be isolated from the stomachs of infected mice, our findings satisfied Koch's postulates. Although further prospective clinical studies are needed, H. suis, like H. pylori, is likely a gastric pathogen in humans. Furthermore, comparative genomic analysis of H. suis using complete genomes of clinical isolates revealed that the genome of each H. suis isolate contained highly plastic genomic regions encoding putative strain-specific virulence factors, including type IV secretion system-associated genes, and that H. suis isolates from humans and pigs were genetically very similar, suggesting possible pig-to-human transmission.

Helicobacter suis and Helicobacter pylori infection in a colony of research macaques: characterization and clinical correlates.

Introduction. Helicobacter suis (Helicobacter heilmannii type 1) commonly infects nonhuman primates but its clinical importance is in question.Aim. To characterize H. suis infection in a colony of rhesus macaques (Macaca mulatta) used in cognitive neuroscience research.Hypothesis/Gap Statement. Inquiries into the nature of Helicobacter suis in nonhuman primates are required to further define the organism's virulence and the experimental animal's gastric microbiome.Methodology. Animals with and without clinical signs of vomiting and abdominal pain (n=5 and n=16, respectively) were evaluated by histology, culture, PCR amplification and sequencing, fluorescent in situ hybridization (FISH) and serology. Three of the five animals with clinical signs, an index case and two others, were evaluated before and after antimicrobial therapy.Results. The index animal had endoscopically visible ulcers and multifocal, moderate, chronic lymphoplasmacytic gastritis with intraglandular and luminal spiral bacteria. Antimicrobial therapy in the index animal achieved histologic improvement, elimination of endoscopically visible ulcers, and evident eradication but clinical signs persisted. In the other treated animals, gastritis scores were not consistently altered, gastric bacteria persisted, but vomiting and abdominal discomfort abated.Nineteen of 21 animals were PCR positive for H. suis and five animals were also PCR positive for H. pylori. Organisms were detected by FISH in 17 of 21 animals: 16S rRNA sequences of two of these were shown to be H. suis. Mild to moderate lymphoplasmacytic gastritis was seen in antrum, body and cardia, with antral gastritis more likely to be moderate than that of the body.Conclusion. No clear association between the bacterial numbers of Helicobacter spp. and the degree of inflammation was observed. H. suis is prevalent in this colony of Macaca mulatta but its clinical importance remains unclear. This study corroborates many of the findings in earlier studies of H. suis infection in macaques but also identifies at least one animal in which gastritis and endoscopically visible gastric ulcers were strongly associated with H. suis infection. In this study, serology was an inadequate biomarker for endoscopic evaluation in diagnosis of H. suis infection.

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.