G. Giamporcaro, M. Falcone, San Raffaele Scientific Institute

September 18, 2020

Diabetes affects 140,000 children in Europe with an annual increase of 21,600 new cases and a dramatic socio-economic impact [1]. In most cases, diabetic children are affected by Type 1 diabetes (T1D), an autoimmune disease characterized by increased glycemia caused by the destruction of insulin-producing pancreatic islets, which are destroyed by patients’ own immune system [2]. Type 2 diabetes has a different pathogenesis and it is related to development of insulin resistance due to obesity and sedentary lifestyle and, although it is less frequent than T1D, its incidence in children and adolescents underwent a greater than 10-fold increase over the past decade [3]. Environmental factors that increase the risk to develop T1D and T2D, such as diet, act at the intestinal level possibly by modifying the gut microbiome (the commensal microorganisms that live within our intestine). These modifications lead to gut inflammation (low-grade colitis with no gastrointestinal symptoms) and increased gut permeability that promote inflammation and alterations of the immune system that are found in T1D but also T2D [4,5]. Moreover, the gut microbiome can also alter the absorption of some nutrients and increase the risk to develop obesity and T2D.

Many studies highlighted alterations of the gut microbiome in children affected by T1D or T2D [6,7,8], however it is still unclear which gut microbial profile is specifically associated with inflammation in the gut and systemically. Moreover, the environmental factors that alter the gut microbiome in diabetic children are largely unknown. Preliminary findings indicate that the diet composition, the quality/quantity of exercise and assumption of some drugs (e.g., antibiotics) can affect the gut microbiome profile. In this study we will analyze the gut microbiome in T1D and T2D children and adolescents and simultaneously record dietary habits and lifestyle in order to define environmental factors and dietary/exercise patterns leading to inflammation and diabetes (T1D and T2D) in children. Our clinical and research data will be ingested in a personalized medicine platform to predict the risk to develop T1D/T2D in children based on genetic and environmental factors (genes, microbiome, inflammatory biomarkers, diet, exercise, antibiotics assumption, etc.). The developed platform will be validated in a clinical trial in which pediatricians and medical personnel will modify the diet and lifestyle of children to promote a beneficial anti-inflammatory gut microbiome profile.

References:

1. https://www.worlddiabetesfoundation.org/sites/default/files/Europe.pdf
2. Ilonen, J., Lempainen, J. & Veijola, R. The heterogeneous pathogenesis of type 1 diabetes mellitus. Nat Rev Endocrinol 15, 635-650 (2019).
3. Skyler, J.S., et al. Differentiation of Diabetes by Pathophysiology, Natural History, and Prognosis. Diabetes 66, 241-255 (2017).
4. Rewers, M. & Ludvigsson, J. Environmental risk factors for type 1 diabetes. Lancet 387, 2340-2348 (2016).
5. Kolb, H. & Martin, S. Environmental/lifestyle factors in the pathogenesis and prevention of type 2 diabetes. BMC Med 15, 131 (2017).
6. Tai, N., Wong, F.S. & Wen, L. The role of gut microbiota in the development of type 1, type 2 diabetes mellitus and obesity. Rev Endocr Metab Disord 16, 55-65 (2015).
7. Vatanen, T., et al. The human gut microbiome in early-onset type 1 diabetes from the TEDDY study. Nature 562, 589-594 (2018).
8. Gurung, M., et al. Role of gut microbiota in type 2 diabetes pathophysiology. EBioMedicine 51, 102590 (2020).