Effect of selenium-enriched probiotic on mucosal tissues

• Grant number: 23/00189-8
• Support Opportunities: Scholarships in Brazil - Master
• Start date: June 01, 2023
• End date: May 31, 2025
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Denise Morais da Fonseca
• Grantee: Gabriele Manamy Baba Rodrigues
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 21/06881-5 - Gut-lung axis: understanding the immune dialogue between barrier tissues in the development of disease, AP.JP2

Abstract

The intestine is the largest organ in the body exposed to environmental antigens, including dietary, microbiota and pathogen-derived components, all of them sharing the same spatial location. Because of this, the intestine harbors a complex network of immune cells responsible for sustaining immune homeostasis by tolerating innocuous antigens while inducing immunity against pathogenic challenges. Such mechanisms include regulatory T cells (Treg) that control inflammatory responses and promote oral tolerance and effector T cells (particularly Th17 lymphocytes) that promote tissue-specific barrier immunity, which encompasses specialized epithelia, production of antimicrobial molecules, antibodies and mononuclear phagocytes. Although the intestinal mucosal immune system is constantly shaped by host genetic factors, resident microbiota, dietary habits and exposure to environmental pathogens, the result of these interactions is usually a return to tissue homeostasis. However, breaking the balance between tolerance and barrier immunity can lead to chronic inflammatory diseases, such as inflammatory bowel diseases (IBDs). In the Laboratory of Mucosal Immunology, we study how environmental factors such as dietary changes, probiotics or infection can shape the immune system of the intestinal mucosa, protecting or promoting the development of IBDs. In particular, we found that after the resolution of defined types of acute intestinal infection (such as infection by Yersinia pseudotuberculosis, YP), a permanent remodeling of the immune and lymphatic system takes place in the gastrointestinal tract, which leads to the translocation of the microbiota to the mesentery resulting in chronic local inflammation that blocks tissue-specific canonical responses. This process, called 'immunological scarring', is directly involved in the etiology of IBDs, particularly colitis. For instance, previously infected animals develop an aggressive manifestation of experimental colitis when challenged with DSS. In parallel, results from our group in a study of the immunoregulatory effect of probiotics in a model of experimental autoimmune encephalitis (EAE) show that the probiotic Selemax (an inactive yeast of Saccharomyces cerevisiae enriched with organic selenium) controlled the development of autoimmunity. The EAE control in animals was also associated with the control of the systemic inflammatory manifestations of the disease, such as pulmonary and intestinal inflammation. In this context, considering the ability of the probiotic Selemax to reverse intestinal inflammation during EAE, we hypothesized that Selemax could also act beneficially on the immunological scar induced post YP-infection, protecting animals from the development of severe forms of IBD following infection. Therefore, in this project, we will study the effect of the probiotic Selemax in the reversal of the immunological scar and in the susceptibility to severe colitis after YP infection.