Design of probiotic bacteria to promote digestive and metabolic health

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The gut microbiota plays a key role in strengthening the gut barrier by stimulating protective responses from the human intestine. Loss of epithelial barrier integrity, also known as a leaky gut can lead to low-grade inflammation and is linked to the development of a number of chronic diseases in humans, from inflammatory bowel disease (IBD) and metabolic syndrome/type 2 diabetes to Parkinsons disease, chronic kidney disease and even certain cancers. Because of its far-reaching impact on these chronic diseases, there is an unmet need to develop new strategies to counteract the detrimental systemic consequences of a leaky gut. In this project, we will design probiotic bacteria that will increase the levels of a microbial product, called MDP, which targets a host protein called NOD2. We have shown that NOD2 activation can fight against a leaky gut and promote healing of the intestinal lining after 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-related problems as well as metabolic diseases, such as type 2 diabetes.