Both obesity and Type 1 diabetes (T1D) are multifactorial chronic diseases characterized by inflammation at intestinal and systemic level. Studies in preclinical models and humans demonstrated that T1D and obesity are influenced by commensal gut microbiota composition. Moreover, recent evidence indicates that some dietary components are fundamental to regulate microbiota composition and promote a beneficial metabolic intestinal environment that reduces systemic inflammation.

Diet interacts with the human ‘holobiont’, i.e., commensal microbiota, in a person-specific way. From previous studies, several enterotypes have been strongly associated with long-term diets. In particular, the Prevotella enterotype has been associated with a high-carbohydrate diet, while the Bacteroides enterotype has been associated with a diet rich in animal proteins and fats. [1] A western diet high in fat, added sugars, choline, animal proteins or unhealthy plant based foods (juices, refined grains, sauces, sweetened beverages) [2], has been shown to increase intestinal dysbiosis thus promoting inflammation. On the contrary, the Mediterranean Diet, high in fiber, vegetal protein, polyphenols, vitamins, minerals, anti-inflammatory omega-3 fatty acids, then vegetables, fruits, legumes, nuts, prebiotics, has been demonstrated to protect against inflammation through a restoration of the intestinal microbiota homeostasis.

This anti-inflammatory effect mostly occurs through the effect that specific foods and micro and macronutrients have on the production of metabolites by the gut microbiota. Food components get metabolized by beneficial gut commensal microbiota in the human gut to produce various types of microbial metabolites. Each microbial metabolite activates various pathways responsible for modulation of gut barrier and inflammation through the activation of membrane or nuclear receptors. [3] Dietary fiber, for example, represents a food component that is not digested at the level of the small intestine but passes directly through the ileum and colon, where it is partially or totally degraded by the microorganisms of the intestinal microbiota. As a product of degradation by microorganisms, monosaccharides are then fermented by the microbiota and converted into short-chain fatty acids or SCFAs, i.e. acetic, butyric and propionic acid. Subsequently, these metabolites are released and used by the host with important functions at the level of the organism. Specifically, SCFA induce differentiation of regulatory T cells with tolerogenic functions that reduce inflammation in the gut and systemically. thus reducing SCFAs are mainly produced by Bifidobacteria, Lactobacilli, Roseburia, Eubacteria, Prevotella and Faecalibacterium. Other beneficial metabolites, such as indoles derivatives or microbial tryptophan metabolites which derive from the fermentation of green vegetables, has been shown to induce the AhR ligand activity that regulate a strong tolerogenic pathway thus reducing inflammation. On the other hand, high consumption of red and processed meat increases the risk of atherosclerosis and incurring cardiovascular diseases through an increase in the production of TMAO, a metabolite resulting from the transformation of carnitine by bacteria of the genus Bacteroides, Alistipes, Bilophila, Ruminococcus and Clostridia. More recently, it emerged that secondary bile acids, metabolites that are produced by commensal gut bacteria by modification of primary bile acids, also play important immune regulatory function and can increase differentiation of T regulatory cells and dampen inflammation.

Alterations of the gut microbiota composition have been found in individuals affected by T1D and obesity  and, although a specific “pro-inflammatory” gut microbiota associated with those medical conditions have not been found, it is clear that modification of the gut metabolic environment through dietary intervention can favor immune tolerance and reduce inflammation in T1D and obesity. Although there is not yet a clear correlation between microbiota changes and dietary habits, recent studies have highlighted the capacity of specific food and macro/micronutrients to reduce inflammation by promoting a beneficial microbial metabolic profile.

The Nutrishield project aims at identifying dietary components and other lifestyle features (e.g., stress, physical activity) that can be associated to altered microbiota composition in diabetic and obese children.  For this purpose, metabolomic and metagenomic analysis will allow us to link the presence and relative abundance of microbial species/microbial metabolites to intestinal inflammation, gut barrier damage and pathology (diabetes/obesity) in correlation with specific foods or nutrients. Based on a profile risk of each child related to dietary habits as well as microbiome and metabolome profiling, we will be able to give a nutritional advice (Personalized Nutrition Algorithm) aimed at restoring a beneficial microbiome composition and reducing chronic inflammation associated with extra-intestinal diseases such as Type 1 Diabetes and Obesity.