Probiotics as a therapeutic strategy to improve metabolism and cognition

• Grant number: 24/09905-0
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2024
• End date: October 31, 2025
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Denise Morais da Fonseca
• Grantee: Denise Morais da Fonseca
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Ana Maria Caetano de Faria ; Andreza Fabro de Bem ; Angelica Thomaz Vieira ; Fatima Theresinha Costa Rodrigues Guma ; Geovanni de Morais Lima ; Marcelo Valdemir de Araujo ; Niels Olsen Saraiva Câmara

Abstract

The recent changes in the global dietary patterns has raised an alarming increase in food insecurity, ranging from malnutrition associated with lack of food access to the excessive consumption of ultra-processed foods and unbalanced diets rich in fat and carbohydrates. Such dietary patterns not only increase the risk of obesity and metabolic diseases but also impact brain function, potentially contributing to cognitive decline and dementia. This phenomenon is intrinsically linked to an inflammatory process in the hippocampus orchestrated by microglia, which maintains cerebral homeostasis by acting as a sensor of environmental signals. Recent evidence points to the gut-adipose tissue-brain axis as a regulator of neuroimmune modulation and metabolic adaptations in response to such diets. Indeed, alterations in the composition of the gut microbiota directly impact the enteric and central nervous systems (CNS). This communication can be mediated by microbiota-derived products, metabolites, and/or inflammatory mediators deriving from the intestinal mucosa or adjacent adipose tissues. Therefore, factors that influence adipose tissue inflammation and metabolic dysfunction resulting from dietary changes may also promote cognitive dysfunctions and inflammatory processes in the CNS. Preliminary results obtained for the development of this project indicate that the microbiota altered by certain gastrointestinal pathogens can contribute to the control of diet-induced metabolic diseases that are intrinsically related to dysfunctions of the gut-adipose tissue-brain axis. In this proposal, we will study the role of microbiota-adipose tissue-microglia communication in the metabolic and cerebral dysfunction induced by unbalanced diets, identifying pro-resolving and pro-inflammatory bioactive metabolites. Such bioproducts could be employed as a therapeutic intervention to restore metabolic and cognitive homeostasis and resistance to dementia (AU)