Jauvain Marine, Lepied Gorann, Bénéjat Lucie, Roudier Nathalie, Dussert Christelle, Lehours Philippe, Varon Christine, Bessède Emilie
Bordeaux Institute of Oncology, BRIC U1312, INSERM, University of Bordeaux, Bordeaux, France.
National Reference Centre for Campylobacters & Helicobacters, University Hospital of Bordeaux, Bordeaux, France.
Helicobacter. 2024 Jul-Aug;29(4):e13108. doi: 10.1111/hel.13108.
Helicobacter pylori infection-associated gastric adenocarcinoma is influenced by various factors, including the digestive microbiota. Lactic acid bacteria role in digestive carcinogenesis has been discussed, and some Lactobacillaceae family species have been shown to act against H. pylori-induced inflammation and colonization. However, their effects on H. pylori-related carcinogenesis have not yet been studied. Lactobacillaceae family effects on the epithelial-to-mesenchymal transition (EMT), emergence of cells with cancer stem cell (CSC) properties and the pro-inflammatory response of gastric epithelial cells to H. pylori infection were investigated.
A co-culture model of AGS gastric epithelial cells infected with a carcinogenic strain of H. pylori associated with 18 different probiotic strains candidates were used. Different EMT indicators and CSC properties were studied, including quantification of the mesenchymal phenotype, tumorsphere formation, EMT marker expression, and tight junction evaluation with immunofluorescence microscopy. The effect of the strains on the pro-inflammatory response to H. pylori was also evaluated by quantifying interleukin-8 (IL-8) production using ELISA.
Among the strains tested, Lactobacillus gasseri BIO6369 and Lacticaseibacillus rhamnosus BIO5326 induced a 30.6% and 38.4% reduction in the mesenchymal phenotype, respectively, caused a significant decrease in Snail and Zeb1 EMT marker expression and prevented the loss of tight junctions induced by H. pylori infection. A separate co-culture with a Boyden chamber maintained the effects induced by the two strains. H. pylori-induced IL-8 production was also significantly reduced in the presence of L. gasseri BIO6369 and L. rhamnosus BIO5326.
Lactobacillus gasseri BIO6369 and L. rhamnosus BIO5326 strains decreased epithelial-to-mesenchymal transition and inflammation induced by H. pylori infection, suggesting that these species may have a protective effect against H. pylori-induced gastric carcinogenesis.
幽门螺杆菌感染相关的胃腺癌受多种因素影响，包括消化微生物群。乳酸菌在消化致癌过程中的作用已被讨论，一些乳杆菌科物种已被证明可对抗幽门螺杆菌诱导的炎症和定植。然而，它们对幽门螺杆菌相关致癌作用的影响尚未得到研究。研究了乳杆菌科对上皮-间质转化（EMT）、具有癌症干细胞（CSC）特性的细胞出现以及胃上皮细胞对幽门螺杆菌感染的促炎反应的影响。
使用与18种不同益生菌候选菌株相关的致癌性幽门螺杆菌感染AGS胃上皮细胞的共培养模型。研究了不同的EMT指标和CSC特性，包括间充质表型的定量、肿瘤球形成、EMT标志物表达以及免疫荧光显微镜下紧密连接的评估。还通过酶联免疫吸附测定（ELISA）定量白细胞介素-8（IL-8）的产生来评估这些菌株对幽门螺杆菌促炎反应的影响。
在测试的菌株中，加氏乳杆菌BIO6369和鼠李糖乳杆菌BIO5326分别使间充质表型减少了30.6%和38.4%，导致Snail和Zeb1 EMT标志物表达显著降低，并防止了幽门螺杆菌感染诱导的紧密连接丧失。与博伊登小室单独共培养维持了这两种菌株诱导的效果。在加氏乳杆菌BIO6369和鼠李糖乳杆菌BIO5326存在的情况下，幽门螺杆菌诱导的IL-8产生也显著降低。
加氏乳杆菌BIO6369和鼠李糖乳杆菌BIO5326菌株减少了幽门螺杆菌感染诱导的上皮-间质转化和炎症，表明这些物种可能对幽门螺杆菌诱导的胃癌发生具有保护作用。
