摘要
The intestinal tract is inhabited by a tremendous number of microorganisms,termed the gut microbiota.These microorganisms live in a mutualistic relationship with their host and assist in the degradation of complex carbohydrates.Although the gut microbiota is generally considered beneficial,the vast number of microbial cells also form a permanent threat to the host.Thus,the intestinal epithelium is covered with a dense layer of mucus to prevent translocation of the gut microbiota into underlying tissues.Intestinal mucus is an organized glycoprotein network with a host-specific glycan structure.While the mucus layer has long been considered a passive,host-designed barrier,recent studies showed that maturation and function of the mucus layer are strongly influenced by the gut microbiota.In return,the glycan repertoire of mucins can select for distinct mucosa-associated bacteria that are able to bind or degrade specific mucin glycans as a nutrient source.Because the intestinal mucus layer is at the crucial interface between host and microbes,its breakdown leads to gut bacterial encroachment that can eventually cause inflammation and infection.Accordingly,a dysfunctional mucus layer has been observed in colitis in mice and humans.Moreover,the increased consumption of a low-fiber Western-style diet in our modern society has recently been demonstrated to cause bacteria-mediated defects of the intestinal mucus layer.Here,I will review current knowledge on the interaction between gut bacteria and the intestinal mucus layer in health and disease.Understanding the molecular details of this host–microbe interaction may contribute to the development of novel treatment options for diseases involving a dysfunctional mucus layer,such as ulcerative colitis.
肠道居住着大量微生物,即所谓的肠道菌群。这些微生物与宿主是一种共生关系,可协助宿主降解复杂的碳水复合物。尽管肠道菌群通常被认为是有益的,但大量存在的微生物细胞对宿主来说也是一种永久性的威胁。因此,肠道上皮覆以一层致密的黏液层,以防止肠道菌群进入下层组织。肠道黏液是一种有着宿主特异性多糖结构的糖蛋白网络。黏液层长久以来一直被认为是一种被动的、宿主设计的屏障,但最新研究显示,黏液层的成熟和功能在很大程度上受肠道菌群的影响。反过来,一些黏膜相关的细菌也能特异性地与黏蛋白中的多糖链结合或降解之,将其作为营养来源。由于肠道黏液层处于宿主与微生物相互作用的关键界面,该层结构的损坏会导致肠道菌群的侵入并最终引起炎症和感染。于是我们在结肠炎大鼠模型和结肠炎患者中,可以观察到黏液层的功能丧失。而且,现代社会中低纤维的西方饮食已被证实会引起细菌介导的肠道黏液层结构损害。在此,本文对健康状态和疾病状态下肠道菌群与肠道黏液层之间的相互作用进行阐述。了解宿主与微生物之间相互作用的具体分子机制,或可研发出针对黏液层功能失调相关疾病(如溃疡性结肠炎)新的治疗手段。
基金
B.O.S.is supported by a Long-Term Fellowship from the Human Frontier Science Program(LT000109/2014).
