Evaluation of the role of IL-22 in the modulation of type 1 diabetes by Akkermansia muciniphila supplementation

• Grant number: 23/12630-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2024
• End date: December 31, 2025
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Daniela Carlos Sartori
• Grantee: Brenda Sara de Lima Alves
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 18/14815-0 - Evaluation of the intestinal microbioma profile and of the therapeutic potential of intervention strategies in the immunopathogeny of type 1 and 2 Diabetes, AP.JP2

Abstract

Type 1 diabetes is a metabolic disease of a multisystemic nature, notorious for its clinical presentation characterized by hyperglycemia and propensity to ketoacidosis. This condition results from insulin deficiency, a hormone whose production is compromised due to the response by T cells. In this condition, the organism produces autoantibodies directed to pancreatic beta cells, located in the islets of Langerhans, resulting in a failure in self-tolerance and activation of autoreactive lymphocytes (Abbas et. al. 9th edition). Consequently, continuous hormone replacement therapy becomes essential, highlighting the importance of exploring innovative therapeutic approaches. According to the Brazilian Diabetes Society, Brazil is currently home to more than 13 million individuals living with this disease, which represents 6.9% of its total population. Type 1 diabetes, although often diagnosed in childhood or adolescence, can also affect adults. In addition to predisposing genetic factors, environmental elements have been identified as triggers of the pathological process. One of the potential environmental influences is the disruption of the intestinal epithelial barrier, leading to the release of microbial products, which may be one of these environmental triggers. The human intestine, when in a healthy state, houses a diversity of microorganisms, including fungi, viruses and several families of bacteria. Recently, 16S rRNA gene sequence analysis has revealed a correlation between the composition of the intestinal microbiota and inflammatory diseases, including type 1 diabetes (Oliveira et. al. 2020). In this sense, changes in the configuration of the intestinal microbiota, known as dysbiosis, play a critical role in the pathogenesis of inflammatory diseases. Therefore, investigating the modulation of the intestinal microbiota through the use of prebiotics and probiotics emerges as a relevant strategy, both in the prevention and treatment of inflammatory diseases. Therefore, it is imperative to recognize the crucial role played by probiotics in immunomodulation, which has a substantial impact on regulating dendritic cell (DC) maturation and promoting DCs with tolerogenic characteristics (Rodrigues et. al. 2022). It is worth highlighting the notable influence exerted by the abundance of Akkermansia muciniphila on the anti-inflammatory response, manifested by a considerable increase in cytokines of an inhibitory nature, which can potentially contribute to the improvement of the clinical picture associated with type 1 diabetes (Rodrigues et . al. 2022). In this sense, previous data from our group demonstrated that Akkermansia muciniphila supplementation was able to protect mice against the development of DM1, both in the non-obese diabetic (NOD) mouse model and in the streptozotocin (STZ)-induced model in C57BL/ mice. 6. In the STZ model, the modulation of DM1 in supplemented mice was associated with the induction of tolerogenic dendritic cells and regulatory T lymphocytes in the pancreatic lymph nodes and pancreas. Furthermore, it was observed that diabetic mice had reduced protein expression of the cytokine IL-22 in the colon, which was reversed with A. muciniphila supplementation (unpublished data).