Sáenz José B
Division of Gastroenterology, Department of Medicine, Washington University in St. Louis School of Medicine, St. Louis, MO, United States.
Front Cell Dev Biol. 2021 Nov 12;9:741574. doi: 10.3389/fcell.2021.741574. eCollection 2021.
The human stomach functions as both a digestive and innate immune organ. Its main product, acid, rapidly breaks down ingested products and equally serves as a highly effective microbial filter. The gastric epithelium has evolved mechanisms to appropriately handle the myriad of injurious substances, both exogenous and endogenous, to maintain the epithelial barrier and restore homeostasis. The most significant chronic insult that the stomach must face is (Hp), a stomach-adapted bacterium that can colonize the stomach and induce chronic inflammatory and pre-neoplastic changes. The progression from chronic inflammation to dysplasia relies on the decades-long interplay between this oncobacterium and its gastric host. This review summarizes the functional and molecular regionalization of the stomach at homeostasis and details how chronic inflammation can lead to characteristic alterations in these developmental demarcations, both at the topographic and glandular levels. More importantly, this review illustrates our current understanding of the epithelial mechanisms that underlie the pre-malignant gastric landscape, how Hp adapts to and exploits these changes, and the clinical implications of identifying these changes in order to stratify patients at risk of developing gastric cancer, a leading cause of cancer-related deaths worldwide.
人的胃兼具消化和固有免疫器官的功能。其主要产物胃酸能迅速分解摄入的物质，同时也是一种高效的微生物过滤器。胃上皮细胞已进化出相应机制，以适当处理各种外源性和内源性有害物质，从而维持上皮屏障并恢复内环境稳态。胃必须面对的最严重慢性损伤因素是幽门螺杆菌（Hp），这是一种适应胃部环境的细菌，可在胃内定植并引发慢性炎症和癌前病变。从慢性炎症发展到发育异常，依赖于这种致癌细菌与其胃部宿主之间长达数十年的相互作用。本综述总结了胃在稳态下的功能和分子区域化，并详细阐述了慢性炎症如何导致这些发育界限在地形和腺体水平上发生特征性改变。更重要的是，本综述阐述了我们目前对癌前胃部病变所涉及的上皮机制的理解，幽门螺杆菌如何适应并利用这些变化，以及识别这些变化对于将胃癌风险患者分层的临床意义，胃癌是全球癌症相关死亡的主要原因之一。
