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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.

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