Editorial: The Triple Interaction: Diet, Microbiota and Epigenetics in the Onset and Management of Type 1 Diabetes.

Abstract

Type 1 diabetes (T1D) is an autoimmune disease that leads to the destruction of pancreas s-cells and insulin deficiency. The main determinant of T1D is genetic predisposition, although most children born carrying T1D genetic risk markers do not develop the disease and, as discussed in most of the papers in this collection, genetics cannot fully explain the disease pathogenesis (Hamilton-Williams et al.; Verduci et al.; Kohil et al.; Al Theyab et al.). It becomes more and more apparent that T1D is a complex disease with intermediate phenotypes, many comorbidities, and heterogeneity in its therapeutic responses. This complexity can be due to interaction with diet and lifestyle that ultimately can affect the microbiota and host immune system via epigenetic mechanisms. The Research Topic represented a fantastic opportunity for the scientific community to provide up-to-date knowledge and propose mechanisms explaining the role of gut microbiota as an epigenetics effector in T1D, and how diet and lifestyle can modulate this interaction, opening new opportunities in the diagnosis and management of T1D. Three key areas have been investigated: Role of diet in T1D pathogenesis Epigenetic function of microbiota Therapeutic prospective. Diet and T1D Pathogenesis Different types of diets may have a protective role against T1D, among those the gluten-free diet (Al Theyab et al.; Hamilton-Williams et al.) and the Mediterranean diet (MD), thanks to its anti-inflammatory properties (Calabrese et al.). On the contrary, a diet high in sugar can increase the risk of T1D, replacing fibers with sugar, which has a detrimental effect on the gut microbiota (Hamilton-Williams et al.). Confirmatory data comes from trials with high fiber diets that showed improvement in the BMI and blood pressure of T1D patients (Kohil et al.). Diets enriched in short-chain fatty acids (SCFA), (Al Theyab et al.) as well as in omega-3 fatty acids (Hamilton-Williams et al.; Kohil et al.), have been reported as potentially beneficial for T1D and islet autoimmunity (IA) by improving bacterial composition. Among the micronutrients, vitamin A deficiency alters the ratio of Firmicutes to Bacteroides and increases the inflammatory response. Iron and zinc also affect microbial composition and the inflammatory response (Al Theyab et al.). Surprisingly, there are contrasting findings on the effect of vitamin D deficiency in T1D (Kohil et al.) and on the gut microbiota (Hamilton-Williams et al.; Calabrese et al.). All these mechanisms can link diet with the etiopathogenesis of T1D, with special attention to early nutrition and specific dietary patterns, such as MD and gluten-free diets, can be explored as therapeutic approaches. Early Nutrition T1D development has been shown to be affected by maternal diet during pregnancy, breastfeeding, and the early introduction of certain foods in infancy. Gut microbiota is also strongly influenced by these factors and their modification impacts on the immune system. A review of the current literature by Verduci et al. encourages long-term breastfeeding and a careful introduction of complementary foods (at 4 months) and cows' milk (at 12 months) to reduce the risk of T1D. Potential mechanisms include the breastmilk nutrients and hormones [human milk oligosaccharides (HMO), leptin, insulin, etc.] that contribute to the maturation of the immune system and the gut microbiota, the increased gut permeability and gut inflammation associated with the early introduction of cow milk vs. the intake of fermented milk products that increase the genera Bifidobacteria and improve the glycemic indexes in animal diabetes models, and finally complementary foods which also accelerate microbiota maturation and diversity impacting on the gut barrier permeability (Verduci et al.). The early gluten introduction also takes a central place in the discussion on the role of diet in T1D pathogenesis, with many common mechanisms between T1D and celiac disease (Verduci et al.; Hamilton-Williams et al.).