Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada.
Gastrointestinal Diseases Research Unit, Kingston General Hospital, Queen's University, Kingston, Ontario, Canada.
Gut Microbes. 2023 Jan-Dec;15(1):2181922. doi: 10.1080/19490976.2023.2181922.
Proteases are an evolutionarily conserved family of enzymes that degrade peptide bonds and have been implicated in several common gastrointestinal (GI) diseases. Although luminal proteolytic activity is important for maintenance of homeostasis and health, the current review describes recent advances in our understanding of how overactivity of luminal proteases contributes to the pathophysiology of celiac disease, irritable bowel syndrome, inflammatory bowel disease and GI infections. Luminal proteases, many of which are produced by the microbiota, can modulate the immunogenicity of dietary antigens, reduce mucosal barrier function and activate pro-inflammatory and pro-nociceptive host signaling. Increased proteolytic activity has been ascribed to both increases in protease production and decreases in inhibitors of luminal proteases. With the identification of strains of bacteria that are important sources of proteases and their inhibitors, the stage is set to develop drug or microbial therapies to restore protease balance and alleviate disease.
蛋白酶是一类进化上保守的酶家族，可降解肽键，与多种常见的胃肠道 (GI) 疾病有关。尽管腔内蛋白水解活性对于维持体内平衡和健康很重要，但本综述描述了我们对腔内蛋白酶过度活跃如何导致乳糜泻、肠易激综合征、炎症性肠病和 GI 感染的病理生理学的最新认识。腔内蛋白酶（其中许多由微生物群产生）可以调节膳食抗原的免疫原性，降低粘膜屏障功能，并激活促炎和促伤害性宿主信号。蛋白酶活性的增加归因于蛋白酶产生的增加和腔内蛋白酶抑制剂的减少。随着鉴定出重要的蛋白酶及其抑制剂来源的细菌菌株，为开发药物或微生物治疗方法以恢复蛋白酶平衡和缓解疾病奠定了基础。
