Daniela Carlos Sartori

(Professor)

Email: danicar@usp.br

Lattes: http://lattes.cnpq.br/2315282418163659

Line of Research: Immunoregulation of Metabolic Diseases

Project: Unpacking the role of the intestinal microbiota at the maternal-fetal interface: biomarkers and therapeutic agents for inflammatory and neurological conditions

Project description: The formation of the human intestinal microbiota begins during the intrauterine period and continues throughout the subsequent phases of extrauterine life. The microbiota plays a fundamental role in the predisposition and non-development of allergic, autoimmune diseases, as well as in various inflammatory processes. It is important to highlight that adequate colonization of the fetal intestinal system is influenced by the maternal microbiota, the type of delivery and the subsequent composition of the intestinal microbiota. In the subsequent phases of childhood life, maternal nutrition, diet and antibiotic use influence the state of eubiose versus dysbiose, which determines adequate growth and development from the neonatal period to adult life. Recently, there has been a lot of interest in the interaction between the intestinal microbiota, brain and pancreas, known as the intestine-brain and the intestine-pancreas. There are four proposed pathways through which intestinal bacteria communicate with the central nervous system (CNS): 1) a neural pathway mediated by the vagus nerve; 2) the immunological pathway, which consists of the modulation of the CNS immune system by the intestinal microbiota; 3) the endocrine pathway, through which hormones modulate intestinal permeability and microbiome composition; e 4) via two bacterial metabolites and neuroactive components. These neuroactive substances include neuropeptides, neurotransmitters and short chain fatty acids (SCFAs), all capable of modulating brain function. Probiotics are defined as live microorganisms that can provide benefits to the health of the host when administered in adequate quantities. Various pre-clinical and some clinical studies demonstrate evidence of two modulatory effects of probiotics on the brain, leading to the emergence of a new category called psychobiotics, but their exact action mechanisms are still largely unknown. This proposal, we intend to contribute to the understanding of these mechanisms, exploring the existence of a fifth mechanism with immunoregulatory effects, based on the effect of the maternal intestinal microbiota on the onset/deficiency of inflammatory and neurological diseases, such as endometriosis, type 1 diabetes (DM1), gestational diabetes and predisposition to depression in offspring. This new pathway could be mediated by extracellular vesicles (EV) or exosomes, which are released by bacterial or immunological cells, reaching intestinal sites and acting as immunoregulatory molecules.