Final Report Summary - SYMOBIGUT (Synergy of milk oligosaccharides and Bifidobacterium infantis in modulating gut epithelial cell function; impact on gut barrier function and the brain-gut axis) Executive Summary:Obesity, i.e. excess of fat mass, has different faces in humans, from obviously healthy to severely sick people. Even if psychological and social distress due to obesity should not be neglected, complications of obesity, such as metabolic syndrome and cardiovascular risks, constitute a major economic burden to our societies. Our societal, economical and scientific challenge is therefore to unravel the mechanisms leading to complications of obesity in order to find preventive strategies.Gut-related disorders in obesity are key factors in the development of obesity-related metabolic disorders such as hyperphagia and type 2 diabetes. The role of the microbiota in these gut-related disorders is also emerging. The objectives of the SYMOBIGUT project were to acquire knowledge and build a professional network on the effect of obesity on intestinal epithelial cells, gut-brain axis regulation of food intake and gut microbiota on one hand and to evaluate the potential of a combination of probiotic (Bifidobacterium infantis) and prebiotic (bovine milk oligosaccharides (BMO)) to alleviate gut epithelial cells disturbances. Different approaches (in vitro and in vivo) were used to study the effect of the combination of B.infantis with BMO on gut barrier function on one hand and on entero-endocrine cells signaling to the brain through the vagus nerve on the other hand. This project was part of a multi-disciplinary project within the Food For Health Institute at UC Davis, California, USA.I established that supplementation of the diet with BMO and B. infantis both prevented or restored gut barrier function in a model of diet-induced obesity in mice. This beneficial effect of this combination is likely due to restoration of gut microbiota and increased level of known beneficial bacteria. I also demonstrated that supernatants obtained from B.infantis culture with BMO but not lactose activates entero-endocrine cells both in vitro and in situ. Gavage of this supernatant to rats resulted in activation of neurons located in nodose ganglia (vagal afferents) and reduction of food intake. Taken together, these final results demonstrate the powerful ability of the combination of B.infantis and BMO to prevent and treat gut-related disorders associated with obesity, i.e. gut barrier function and alteration gut-brain axis signaling.This multi-disciplinary project resulted in a long-term collaboration between the out-going and the return phase groups with exchange of graduate students between labs in the near future. The fellow has now established an independent group with several graduate students and grant application under examination.Expected impact are the use of the combination of probiotic and prebiotic in prevention and treatment of gut-related disorders in obesity on one hand and long-term collaboration between the two labs on the other hand.