Abstract
In a minority of patients with chronic stomach pain, long, spiral-shaped non-Helicobacter pylori helicobacters (NHPH) are found. These helicobacters colonize the stomach of humans and animals (such as dogs, cats and pigs) and are considered to have zoonotic potential. In the past, NHPH have been referred to as H. heilmannii sensu lato group, which includes several species: H. suis, H. felis, H. bizzozeronii, H. salomonis, H. heilmannii, H. cynogastricus and H. baculiformis. Previous work suggests a contributing factor in the etiology of various gastrointestinal diseases, ranging from chronic active gastritis without clinical symptoms to peptic ulceration, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. NHPH bacteria are considered to also play a role in premalignant lesions of gastric cancer such as chronic gastritis, intestinal metaplasia and dysplasia. The exact prevalence of NHPH in these conditions is not clear. According to a recent study of our group, the prevalence of NHPH can vary between 20% to 25% in high risk patients and eradication with antibiotics can induce clinical and histological benefit in some patients. However up till now, 1/ no large multicenter prospective epidemiological studies on NHPH in patients with unexplained gastric disease exist, 2/ nor placebo-controlled randomized eradication studies for gastric NHPHs 3/ nor the impact of NHPH on the structural/functional heterogeneity of the mucin expression have been studied in the past and are therefore subject of the current PhD project. We would therefore link our expertise in mucin research with the topic of NHPHs in gastric disease.
First, we will conduct a descriptive observational cross-sectional study on the prevalence of NHPH in high risk gastric patients. Second, a multicenter placebo-controlled randomized trial with antibiotics (Tryplera®) in NHPH positive patients will be performed in which the success rate of eradication and clinical, endoscopic and histological remission will be evaluated by means of standard genomic sequencing on target gastric biopsies. However, also new non-invasive tools as volatile organic compounds (VOCS) and genomic testing on saliva of patients will be tested for their diagnostic performance. Finally, the dynamics in mucins expression, that drive the evolution to more progressive gastric disease by causing enhanced inflammation and barrier dysfunction, will be studied and linked to the gastric microbial diversity and function (i.e. microbial-mucin mRNA isoform signature) in these well-defined gastric diseases and (pre-) malignancies in NHPH positive patients.
Elucidating the pathogenic role of the NHPH and mucins in these associated diseases, can potentially improve the diagnosis and treatment of NHPH, can be beneficial to halt the progression towards gastric malignancy and can help patients with unexplained gastric symptoms.
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