Antagonistic Activities of Lactobacillus rhamnosus JB3 Against Helicobacter pylori Infection Through Lipid Raft Formation

Abstract

Helicobacter pylori is a Gram-negative pathogen that can increase the risk of stomach cancer in infected patients. H. pylori exploits lipid rafts to infect host cells. Infection triggers clustering of Lewis x antigen (Lex) and integrins in lipid rafts to facilitate H. pylori adherence to the gastric epithelium. H. pylori infection can be treated with probiotics containing lactic acid bacteria that offer numerous benefits to the host while lacking the side effects associated with antibiotic therapy. Previously, we showed that the cell-free supernatant (CFS) derived from Lactobacillus rhamnosus JB3 (LR-JB3) at a multiplicity of infection (MOI) of 25 attenuated the pathogenicity of H. pylori. In this study, we established a mucin model to simulate the gastric environment and to further understand the influence of mucin on the pathogenesis of H. pylori. Porcine stomach mucin dramatically upregulated H. pylori virulence gene expression, including that of babA, sabA, fucT, vacA, hp0499, cagA, and cagL, as well as the adhesion and invasion ability of H. pylori and induced increased levels of IL-8 in infected-AGS cells. The CFS derived from LR-JB3 at a MOI of 25 reduced the expression of H. pylori sabA, fucT, and hp0499 in mucin, as well as that of the Lex antigen and the α5β1 integrin in AGS cells during co-cultivation. These inhibitory effects of LR-JB3 also suppressed lipid raft clustering and attenuated Lewis antigen-dependent adherence, type IV secretion system-mediated cell contact, and lipid raft-mediated entry of VacA to host cells. In conclusion, LR-JB3 could affect H. pylori infection through mediating lipid raft formation of the host cells. The currently unknown cues secreted from LR-JB3 are valuable not only for treating H. pylori infection, but also for treating diseases that are also mediated by lipid raft signaling, such as cancer and aging-associated and neurodegenerative conditions.

Gastric microbiota dysbiosis and Helicobacter pylori infection

“…S. boulardii produces neuraminidase selective for α (2–3)-linked sialic acid to remove H. pylori adhesin ligands, inhibiting H. pylori adherence to host cells ( Sakarya and Gunay, 2014 ). Do et al (2021a , b) used a cell model to show that Lactobacillus rhamnosus JB3 (LR-JB3) reduced H. pylori VacA, sialic acid-binding adhesin (SabA), and fucosyltransferases (FucT) and decreased Lewis (Le) x antigen, toll-like receptor 4 (TLR4) and α5β1 integrin expression in AGS cells. Therefore, it further suppressed lipid raft clustering and attenuated Lewis antigen-dependent adherence, T4SS-mediated cell contact, and lipid-raft-mediated VacA entry into host cells ( Do et al, 2021a , b ).…”

Therapeutic Approach Targeting Gut Microbiome in Gastrointestinal Infectious Diseases

“…Studies on the immunomodulatory effects of Lactobacillus demonstrated that some strains could modulate immune reactions and alleviate inflammation by reducing the production of several pro-inflammatory cytokines, notably IL-8 [42], and stimulating the production of immunoregulatory cytokine IL-10 [43]. Do et al proposed that Lactobacillus rhamnosus strain JB3 could inhibit the attack of H. pylori on host cells by mitigating lipid raft formation, which might be hijacked by H. pylori during infection [44]. One strain of Parabacteroides golsteinii was reported to have the ability to modify gut microbiota and reduce cholesterol levels, which helps reduce H. pylori toxicity [45].…”

Inhibitory activity of Limosilactobacillus reuteri isolated from camel milk against Helicobacter pylori effects in human gastric epithelial cells

“…Probiotics, nonpathogenic microbial feed or food supplements, are already widely investigated as an intelligent alternative to dealing with H. pylori 7 . The anti‐ H. pylori activity of probiotics is previously reported by several investigators 7–12,3 . Lee et al 13 .…”

“…7 The anti-H. pylori activity of probiotics is previously reported by several investigators. [7][8][9][10][11][12]3 Lee et al 13 reported the antiinflammatory effects of lactobacilli probiotics against H. pylori infection via moderating the suppressor of cytokine signaling expression. The other studies reported a potent anti-H. pylori activity for Limosilactobacillus fermentum UCO-979C.…”