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.
Highlights
H. pylori has presumably co-evolved with humans for at least 50,000 years to be transmitted from person to person and become a commensal of the stomach [1,2]
We showed that mixed infections were less frequent in Gastric Cancer (GC) (OR = 0.10; 95% confidence intervals (CI): 0.02–0.48, p = 0.004) and First Degree Relatives (FDR) groups (OR = 0.16; 95% CI: 0.03–0.81, p = 0.03) compared to D, whereas no statistically significant difference was observed for Autoimmune Gastritis (AG)
Consistent with data reported in the literature [49,51,52,53], GC patients included in this study showed an association with H. pylori strains harboring the Cytotoxin-associated gene-A Pathogenicity Island (CagPAI), which was accompanied by the presence of the highly virulent forms of the vacA gene, in accordance with previously reported data [54,55]
Summary
H. pylori has presumably co-evolved with humans for at least 50,000 years to be transmitted from person to person and become a commensal of the stomach [1,2]. H. pylori has been classified as a class I human carcinogen by the International Agency for Research on Cancer working group for its association, in particular, with non-cardia gastric cancer (GC) and mucosa-associated lymphoid tissue (MALT) lymphoma [3]. The mechanisms by which H. pylori may express its pathogenetic potential is related to bacterial structure and induced chronic inflammation, that triggers chronic active gastritis and development of GC lesions according the currently accepted model of precancerous Correa’s cascade (in order, non-atrophic gastritis, multifocal atrophic gastritis, intestinal metaplasia, dysplasia and, cancer) [5]. Histopathological changes in the gastric mucosa can be associated with H. pylori fitness adaptation through multiple and subtle genetic events which allow its persistence in the microenvironment [6]. Each host is colonized by a multitude of genetically closely related microorganisms, similar to quasispecies, which interfere with signaling pathways influencing host cell growth and death [7,8,9]
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