Role of bactericidal permeability increasing protein (BPI) in bidirectional hostmicrobiota communication in the gut

杀菌通透性增加蛋白（BPI）是一种具有最高亲和力的脂多糖结合蛋白，对革兰氏阴性菌具有较强的抗菌活性。BPI由髓系造血细胞（如中性粒细胞）和上皮细胞（包括胃肠道细胞）表达。除了作为一种非常有效的内源性抗生素外，最近的研究表明，BPI中和自身抗体以及BPI基因多态性（Lys216Glu）与炎症性肠病（IBD、克罗恩病和溃疡性结肠炎）有关。我们的目的是研究BPI在稳态和炎症条件下稳定肠道微生物群和胃肠道粘膜表面相互关系的作用。应用新生成的BPI基因缺陷小鼠和BPI人源化的bac转基因小鼠，将探讨微生物群对BPI粘膜表达的影响，以及BPI在塑造微生物群组成中的作用，III)它们与宿主粘膜的空间分离，以及IV)肠道细菌驱动炎症过程的控制。更好地了解BPI在微生物-宿主双向相互作用中的作用将为未来炎症性肠病的治疗策略提供基础。

Bactericidal permeability increasing protein (BPI) has been characterized as LPS-binding protein with the highest affinity and displays strong antimicrobial activities against Gram negative bacteria. BPI is expressed by myeloid hematopoietic cells such as neutrophils and by epithelial cells including those of the gastrointestinal tract. Besides its features as very potent endogenous antibiotic, recent studies have shown that BPIneutralizing autoantibodies as well as BPI gene polymorphisms (Lys216Glu) are associated with inflammatory bowel diseases (IBD, Crohn´s disease and ulcerative colitis). We aim to investigate the role of BPI for stabilizing the interrelationship of gut microbiota and the gastrointestinal mucosal surface in homoeostatic and inflammatory conditions. Applying newly generated BPI gene-deficient as well as BPI-humanized BAC-transgenic mice I) the influence of microbiota on the mucosal expression of BPI as well as II) the role of BPI for shaping the microbiota composition, III) their spatial segregation from the host mucosa and IV) the control of bacteria-driven inflammatory processes in the gut will be addressed. A better understanding of the role of BPI in the bidirectional microbiota-host interaction will provide the basis for future therapeutic strategies in inflammatory bowel diseases.