Design of probiotic bacteria to promote digestive and metabolic health

肠道微生物区系通过刺激人体肠道的保护性反应，在加强肠道屏障方面发挥着关键作用。上皮屏障完整性的丧失，也称为肠漏，可导致低度炎症，并与人类许多慢性疾病的发展有关，从炎症性肠病(IBD)和代谢综合征/2型糖尿病到帕金森氏病、慢性肾脏疾病，甚至某些癌症。由于它对这些慢性疾病的深远影响，迫切需要开发新的战略来抵消肠道漏出的有害系统性后果。在这个项目中，我们将设计益生菌，以增加非微生物产品MDP的水平，MDP针对的是一种名为NOD2的宿主蛋白。我们已经证明，激活NOD2可以对抗肠漏，并促进损伤后肠道衬里的愈合。同时，NOD2的激活也可以改善代谢健康。因此，这些益生菌可以用于保护和治疗与肠道相关的问题以及代谢性疾病，如2型糖尿病。

The gut microbiota plays a key role in strengthening the gut barrier by stimulating protectiveresponses from the human intestine. Loss of epithelial barrier integrity, also known as a leakygut can lead to low-grade inflammation and is linked to the development of a number ofchronic diseases in humans, from inflammatory bowel disease (IBD) and metabolicsyndrome/type 2 diabetes to Parkinsons disease, chronic kidney disease and even certaincancers. Because of its far-reaching impact on these chronic diseases, there is an unmetneed to develop new strategies to counteract the detrimental systemic consequences of aleaky gut. In this project, we will design probiotic bacteria that will increase the levels of amicrobial product, called MDP, which targets a host protein called NOD2. We have shownthat NOD2 activation can fight against a leaky gut and promote healing of the intestinal liningafter injury. At the same time, NOD2 triggering can also improve metabolic health.Consequently, these probiotics could be used to protect and treat individuals with gut-relatedproblems as well as metabolic diseases, such as type 2 diabetes.