This article focuses on the pathogenic significance ofHelicobacterspecies naturally colonizing the stomach of dogs, cats and pigs. These gastric “non-Helicobacter(H.)pylori Helicobacterspecies” (NHPH) are less well-known than the human adaptedH. pylori.Helicobacter suishas 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 thepars oesophageaof the porcine stomach.The stomach of dogs and cats can be colonized by severalHelicobacterspecies but their pathogenic significance for these animals is probably low.Helicobacter suisas well as several canine and feline gastricHelicobacterspecies 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, forH. suis, also consumption of contaminated pork. It has been described that standardH. pylorieradication therapy is usually also effective to eradicate the NHPH in human patients, although acquired antimicrobial resistance may occasionally occur and porcineH. suisstrains are intrinsically less susceptible to aminopenicillins than non-human primateH. suisstrains and other gastricHelicobacterspecies. Virulence factors ofH. suisand the canine and feline gastricHelicobacterspecies 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 inH. pylori.It can be concluded that besidesH. pylori, gastricHelicobacterspecies 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.

Summary: Background: Gastric non‐Helicobacter pylori Helicobacter (NHPH) species naturally associated with animals have been linked with gastric disease in human patients.Aim: The prevalence and clinical significance of zoonotic gastric NHPHs was determined in large and well‐defined, H. pylori‐negative, gastric patient populations.Methods: Patients were retrospectively (n = 464) and prospectively (n = 65) included for gastric biopsy collection: chronic gastritis (CG), peptic ulcer disease and gastric MALT lymphoma, without identified aetiology. PCR and sequencing was performed for the detection of gastric Helicobacter species. Retrospectively, asymptomatic gastric bypass patients (n = 38) were included as controls. Prospectively, additional saliva samples and symptom and risk factor questionnaires were collected. In this group, patients with gastric NHPH infection were administered standard H. pylori eradication therapy and underwent follow‐up gastroscopy post‐therapy.Results: In the retrospective samples, the prevalence of gastric NHPHs was 29.1%, while no gastric NHPHs were detected in control biopsies. In the prospective cohort, a similar proportion tested positive: 27.7% in gastric tissue and 20.6% in saliva. The sensitivity and accuracy for the detection of gastric NHPHs in saliva compared to gastric tissue was 27.8% and 69.8% respectively. Following eradication therapy, clinical remission was registered in 12 of 17 patients, histological remission in seven of nine and eradication in four of eight patients.Conclusion: These findings suggest a pathophysiological involvement of NHPHs in gastric disease. Patients presenting with gastric complaints may benefit from routine PCR testing for zoonotic gastric NHPHs.

The genus Helicobacter is composed of bacteria that colonize both the human and animal gastrointestinal tract. Helicobacter pylori infects half of the world’s population, causing various disorders, such as gastritis, duodenitis and gastric cancer. Additionally, non-Helicobacter pylori Helicobacter species (NHPH) are commonly found in the stomach of pigs, dogs and cats. Most of these species have zoonotic potential and prevalence rates of 0.2–6.0%, and have been described in human patients suffering from gastric disorders undergoing a gastric biopsy. The aim of this study was to determine the occurrence of Helicobacter spp. in the stomach of patients with gastric cancer (n = 17) and obese (n = 63) patients. Furthermore, the outcome of the Helicobacter eradication treatment and the current infection status was evaluated. Overall, based on the genus-specific PCR followed by sequencing, DNA from Helicobacter spp. was detected in 46.3% of the patients, including single infections with H. pylori in 43.8% of the patients and mixed infections with H. pylori and canine- or feline-associated H. felis in 2.5%. About 32.5% of the patients had been subjected to previous Helicobacter eradication therapy and the triple standard therapy was the most frequent scheme (42.3%). In 48.0% of the patients who received eradication treatment, bacteria were still detected, including one mixed infection. In 23.1% of the patients who reported that a subsequent test had been performed to confirm the elimination of the bacteria, Helicobacter were still detected. In conclusion, although in a smaller percentage, NHPH may also be present in the human stomach. Thus, specific NHPH screening should be included in the diagnostic routine. The continued presence of H. pylori in the stomach of patients recently subjected to eradication schemes raises questions about the efficacy of the current Helicobacter treatments.

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.

While seven gastric non-Helicobacter pylori Helicobacter (NHPH) species are known to commonly colonize the stomach of cats and dogs, the potential of H. pylori and H. pylori-like organisms to infect animals remains controversial and was investigated in this study using gastric samples of 20 cats and 27 dogs. A Helicobacter genus-specific 16 S rRNA PCR assay, H. pylori-specific ureAB and glmM PCR assays and a nested PCR detecting 23 S rRNA in a Helicobacter genus-specific manner in a first round of PCR and a H. pylori-specific manner in a second round, were performed in combination with sequencing. Histopathological and anti-Helicobacter immunohistochemical evaluations were also performed. Based on 16 S rRNA sequence analysis, 39/47 animals (83%) appeared infected with canine/feline gastric NHPHs in the corpus and/or antrum. H. pylori-specific ureAB amplicons were obtained in samples of 22 stomachs (47%). One canine antrum sample positive in the ureAB assay was also positive in the H. pylori-specific glmM assay. While 36/47 (77%) animals had a positive sample in the first round of the nested 23 S rRNA PCR assay, all samples were negative in the second round. Sequence analysis of obtained amplicons and immunohistochemistry point towards the presence of unidentified H. pylori-like organisms in cats and dogs. Histopathological examination suggests a low pathogenic significance of the gastric Helicobacter spp. present in these animals. In conclusion, cats and dogs may be (co-)infected with gastric Helicobacter organisms other than the known gastric NHPHs. Culture and isolation should be performed to confirm this hypothesis.

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.