Lactobacillus gasseri suppresses the Helicobacter pylori-induced expression of the proliferation-associated factors HBEGF and TGF-α in gastric host cells

To date, various probiotic lactobacilli have been tested against Helicobacter pylori. However, a detailed molecular analysis of the various signaling pathways and their associated anti-proliferative activity remains poorly understood. In our previously published research, a disintegrin and metalloprotease 17 (ADAM17) was proposed as a key target for anti-inflammatory activity in H. pylori-infected host macrophages. Therefore, in this study, the anti-H. pylori activity of selected lactobacilli was assessed based on expression of ADAM17 and two of its targets, heparin-binding EGF-like growth factor (HBEGF) and transforming growth factor-alpha (TGF-α), which were measured in gastric epithelial cells. For this purpose, lactobacilli and H. pylori were either added together to the AGS cells (coincubation), or the cells were first exposed to lactobacilli before H. pylori infection (preincubation). In coincubation assays, lactobacilli had no effect on H. pylori-mediated ADAM17, HBEGF, and TGF-α upregulation at the protein level. However, in preincubation assays, L. gasseri downregulated the expression of ADAM17 and its substrates. Furthermore, the proliferation data demonstrated that L. gasseri suppressed H. pylori-induced cellular progression. Using an in vivo mouse model, the anti-inflammatory activity of selected lactobacilli was tested by measuring blood cytokine profiles and tissue staining. L. gasseri significantly decreased the levels of the pro-inflammatory cytokine TNF and reduced immune cell infiltration in stained gastric tissues. Together, these findings suggest that certain lactobacilli can counteract the H. pylori-mediated induction of HBEGF and TGF-α expression, and indicate that ADAM17 could be targeted to inhibit the cancer-related effects of H. pylori.