Microbiota-immune interactions that promote intestinal homeostasis

摘要 炎症性肠病(IBD)患者更容易出现代谢异常，例如 然而，人们对这种联系的基础知之甚少。多项研究现已表明 微生物区系组成的变化是多种疾病的一个因素，包括IBD和糖尿病。 此外，研究了IBD或IBD患者体内微生物群组成的研究 糖尿病，也发现了这些居民社区类似的变化。我们最近发现了一只老鼠 模型发展恶化结肠炎、自发性肥胖和胰岛素抵抗。这两种疾病 依赖于微生物区系，可以通过微生物区系移植或口服纯化的 梭状芽胞杆菌种群。因此，我们假设IBD和糖尿病发病率的增加可能是 可归因于微生物区系中类似的缺陷，这可能解释了为什么一些人更容易 两种疾病都会发生。基于此，我们提出了一系列实验，以确定一个定义的财团 梭状芽胞杆菌将起到预防疾病和探索常见机制的作用，包括 免疫系统，介于IBD和新陈代谢之间，可能导致这些疾病的发展。因此，我们的 这一发现将是第一批确定可用于治疗的细菌组合之一。 干预/预防IBD和/或糖尿病，并允许深入了解机制如何 这些保护性细菌维持肠道内环境的稳定。

ABSTRACT Individuals with inflammatory bowel disease (IBD) are more likely to develop metabolic abnormalities, such as diabetes, however little is known about the basis of this connection. Multiple studies have now shown that changes to the composition of the microbiota are a factor in multiple diseases, including IBD and diabetes. Moreover, the studies that have examined the composition of the microbiota within individuals with IBD or diabetes, have identified similar changes to these resident communities. We have recently identified a mouse model that develops worsened colitis and spontaneous obesity and insulin resistance. Both of these diseases are reliant on the microbiota and can be rescued by a microbiota transplant, or an oral gavage of a purified population of Clostridia. Thus, we hypothesize that the growing incidence of IBD and diabetes may be attributable to similar defects in the microbiota and might explain the why some individuals are more prone to develop both diseases. Based on this, we propose a series of experiments to identify a defined consortia of Clostridia that will function to prevent disease and explore the common mechanisms, including effects of the immune system, between IBD and metabolism that might lead to the development of these diseases. Thus, our findings will be among the first to identify a consortia of bacteria that could be used for therapeutic intervention/prevention of IBD and/or diabetes and allow for an in-depth mechanistic understanding of how these protective bacteria maintain intestinal homeostasis.