Aim protein-based anti-inflammatory therapeutic for the treatment of IBD

炎症性肠病(IBD)，分为溃疡性结肠炎(UC)和克罗恩病 疾病(CD)是世界范围内流行且日益严重的临床健康问题。这些 疾病的特征是虚弱的症状，包括腹泻、腹痛和 疲劳，并增加患胃肠道癌症的风险。此外，IBD患者还受到了 肠道微生物群，称为生物失调。炎症性肠病病因复杂 免疫遗传变异、环境因素和肠道之间的相互作用 微生物组。目前治疗IBD的方法包括皮质类固醇和生物制剂，它们可以改善 过度产生促炎细胞因子和其他炎症介质，但它们确实 不治疗经常引发或传播炎症的微生物群失调。此外，龙 长期使用皮质类固醇和生物制剂有严重的副作用，包括骨质疏松症、消化系统疾病 溃疡、胰腺炎和伤口愈合不良。因此，迫切需要更多 治疗炎症性肠病的有效疗法，既能治疗炎症，又能治疗微生物群失调。的一项功能 IBD UC亚型是炎性结肠组织中高水平的中性粒细胞聚集和 对滞留的结肠微生物的过度嗜中性反应。我们的研究团队在 由KeyBiome创始人领导的俄勒冈大学发现了一种新的抗炎药物 斑马鱼肠道共生菌Aeromonas分泌的蛋白质，我们将其命名为免疫气单胞菌 调制器(AIMA)。我们已经证明了艾玛具有有效的抗炎作用。 通过减少肠道中性粒细胞。此外，我们有证据表明艾玛有微生物群- 调节活性，包括抑制促炎细菌种类的生长。 因此，AIMA提供了一个机会来开发一种治疗IBD的药物，其独特的能力在于 两者都以炎症的主要介质中性粒细胞为靶点，并促进 微生物群生态失调。在这个项目中，我们将为AIMA的治疗建立概念验证数据 IBD小鼠模型的疗效和微生物组调节活性。这将激励未来 AIMA开发成为一种新的人类治疗方法，为IBD患者提供更多 有效和更安全的替代目前的治疗方法。

Inflammatory bowel disease (IBD), which is subdivided into ulcerative colitis (UC) and Crohn’s disease (CD), constitutes a prevalent and growing clinical health problem worldwide. These diseases are characterized by debilitating symptoms including diarrhea, abdominal pain, and fatigue, and increased risk of gastrointestinal cancers. In addition, IBD patients have perturbed intestinal microbiomes, referred to as dysbiosis. The etiology of IBD involves complicated interactions between immunological genetic variants, environmental factors, and the intestinal microbiome. Current therapies for IBD include corticosteroids and biologics, which can ameliorate overproduction of pro-inflammatory cytokines, and other inflammatory mediators, but which do not treat the microbiome dysbiosis that often triggers or propagates inflammation. In addition, long term use of corticosteroids and biologics has serious side effects, including osteoporosis, peptic ulcers, pancreatitis, and impaired wound healing. Therefore, an urgent need exists for more effective therapies for IBD that treat both inflammation and microbiome dysbiosis. A feature of the IBD subtype UC is the accumulation of high levels of neutrophils in inflamed colonic tissues and an excessive neutrophilic response to resident colonic microbes. Our research team at the University of Oregon, led by the founders of KeyBiome, has identified a novel anti-inflammatory protein secreted by a zebrafish gut symbiont, Aeromonas, which we named Aeromonas immune modulator (AimA). We have shown that AimA has potent anti-inflammatory properties, indicated by a reduction in intestinal neutrophils. Moreover, we have evidence that AimA has microbiome- modulating activities that include growth inhibition of pro-inflammatory bacterial species. Therefore, AimA presents an opportunity to develop a therapeutic for IBD, unique in its ability to both target a primary mediator of inflammation, neutrophils, and facilitate restoration of microbiome dysbiosis. In this project we will establish proof of concept data for AimA’s therapeutic efficacy and microbiome-modulating activity in a mouse model of IBD. This will motivate future development of AimA into a novel human therapeutic to offer patients suffering from IBD a more effective and safer alternative to current therapies.