Contextual effect and safety of probiotic consumption in intestinal inflammatory processes

• Grant number: 25/01138-3
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: August 01, 2025
• End date: May 31, 2028
• Field of knowledge: Biological Sciences - 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 intestinal mucosa is constantly exposed to various environmental antigens, originating from pathogens or harmless sources such as dietary components or antigens from the commensal microbiota, which affect immunological homeostasis. Therefore, the immune system associated with the intestinal mucosa requires a complex cellular network of highly regulated mechanisms to maintain tissue balance and, at the same time, protect against the entry of pathogens. Such mechanisms include CD103+CD11b- and CD103+CD11b+ dendritic cells (DCs), which induce canonical responses in the intestine, as well as regulatory T cells (Treg) that control inflammatory responses and promote tolerance to harmless antigens and effector cells (particularly lymphocytes). Th17) that promote tissue-specific barrier immunity. This barrier response encompasses specialized epithelia, the 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 outcome of these interactions is typically a return to tissue homeostasis. However, a breakdown in the balance between tolerance and barrier immunity can generate chronic inflammatory diseases, such as inflammatory bowel diseases (IBDs). At the Mucosal Immunology Laboratory, we study how environmental factors, whether changes in diet, consumption of probiotics, or episodes of infection, shape the immune system associated with the intestinal mucosa. Previous results obtained by our group show that, in a murine model using animals of the C57BL/6 lineage, after the resolution of the infection caused by the bacterium Yersinia pseudotuberculosis (YP), there is a remodeling of the immune and lymphatic systems of the gastrointestinal tract, leading to the translocation of microbiota to the mesentery and consequent local chronic inflammation that blocks canonical tissue-specific responses. This process, which we call "immunological scarring", contributes to the development of IBD. Aiming to revert the immunological scar to immune homeostasis or prevent its establishment, we performed pre- and post-infection treatment with two different supplements: (1) an inactivated Saccharomyces cerevisiae strain enriched with selenium (Se) and (2) the active yeast S. cerevisiae (SC) (strain UFMG A-905). The results obtained during the master's degree showed that post-infection treatment with the yeast SC UFMG A-905, contrary to our initial hypothesis, aggravated chronic inflammation in previously infected animals, indicated by increased recruitment of neutrophils and Th1 to the mesentery and mesenteric lymph nodes (MLNs) post-infection. We also observed that none of the treatments was sufficient to restore the integrity of the mesenteric lymphatic vessels since the treated animals also presented reduced frequency of CD103+CD11b- and CD103+CD11b+ DCs in the MLNs. Based on these results, we hypothesize that treatment with SC UFMG A-905, before or after infection, could increase the susceptibility to more severe forms of experimental colitis caused by DSS. Given this context, the new objective of the present project is to evaluate in which situations treatment with probiotics should not be recommended. (AU)