Differential Helicobacter pylori Plasticity in the Gastric Niche of Subjects at Increased Gastric Cancer Risk

Abstract

Helicobacter pylori (H. pylori) represents an independent risk factor for Gastric Cancer (GC). First Degree Relatives (FDR) of GC subjects and Autoimmune Gastritis (AG) patients are both at increased risk for GC. H. pylori genetic heterogeneity within the gastric niche of FDR and AG individuals has been little explored. To understand whether they exploit an increased H. pylori stability and virulence, 14 AG, 25 FDR, 39 GC and 13 dyspeptic patients (D) were investigated by a cultural PCR-based approach characterizing single colonies-forming-units. We chose three loci within the Cytotoxin-associated gene-A Pathogenicity Island (CagPAI) (cagA,cagE,virB11), vacA, homA and homB as markers of virulence with reported association to GC. Inflammatory/precancerous lesions were staged according to Sydney System. When compared to D, FDR, similarly to GC patients, were associated to higher atrophy (OR = 6.29; 95% CI:1.23–31.96 in FDR; OR = 7.50; 95% CI:1.67–33.72 in GC) and a lower frequency of mixed infections (OR = 0.16; 95% CI:0.03–0.81 in FDR; OR = 0.10; 95% CI:0.02–0.48 in GC). FDR presented also an increased neutrophil infiltration (OR = 7.19; 95% CI:1.16–44.65). Both FDR and GC carried a higher proportion of CagPAI+vacAs1i1mx+homB+ profiles (OR = 2.71; 95% CI: 1.66–4.41 and OR = 3.43; 95% CI: 2.16–5.44, respectively). Conversely, AG patients presented a lower frequency of subtypes carrying a stable CagPAI and vacAs1i1mx. These results underline different H. pylori plasticity in FDR and AG individuals, and thus, a different host-bacterium interaction capacity that should be considered in the context of eradication therapies.

Correlation between the geographical origin of Helicobacter pylori homB-positive strains and their clinical outcomes: a systematic review and meta-analysis

“…Using the Newcastle-Ottawa Scale (NOS), 12 eligible studies were selected (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). Required information such as rst author, year of publication, country, population sample size, number of H.pylori strains, Frequency of homB in strains creating different clinical futures, diagnostic methods and reference number are listed in Table 1.…”

“…In total, out of 12 studies that met our inclusion criteria, 2930 patients and 2016 strains of H. pylori were evaluated. Of these, two studies compared the relationship between homB and clinical outcomes in both Western and Asian countries (22,24), Six studies have been conducted on Western countries (19,20,23,(27)(28)(29), as well as four studies on the population of Asia (21,25,26,30) ( Table 1). Final results of some of eligible studies were contradictory and varied (20,22,24,25).…”

Matrix Metalloproteinases in Helicobacter pylori–Associated Gastritis and Gastric Cancer

“…In combination with other inflammation-associated virulence factors, CagA essentially contributes to severe gastric pathology [26]. CagPAI-and CagA-expressing H. pylori strains are strongly associated with gastritis and gastric adenocarcinoma development [27]. The intermediates of the lipopolysaccharide biosynthesis HBP (heptose 1,7-bisphosphate) and its more abundant and potent derivative, ADP-glycero-β-D-manno-heptose (ADP-heptose), are involved in the activation of NF-κB [28][29][30].…”

Immunological Aspects of the Tumor Microenvironment and Epithelial-Mesenchymal Transition in Gastric Carcinogenesis

“…Because of its invasive properties, H. pylori is thought to be responsible for one of the highest rates of chronic infections worldwide. Several virulence factors of H. pylori contribute to the stomach invasion and development of GC [28][29][30]. These include cytotoxin-associated gene A (CagA), vacuolating cytotoxin (VacA), or outer inflammatory protein A (OipA) [31].…”