Involvement of the Microbiota in the Effects of Cannabidiol in an Animal Model of Autism

• Grant number: 23/16731-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: October 01, 2024
• End date: October 31, 2027
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Francisco Silveira Guimaraes
• Grantee: Lucas Hassib Camina
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 17/24304-0 - New perspectives in the use of drugs that modify atypical neurotransmitters in the treatment of neuropsychiatric disorders, AP.TEM

Abstract

Interactions between the gut microbiota and the Central Nervous System (CNS) play a significant role in Autism Spectrum Disorder (ASD), highlighting the Gut-Brain-Microbiota Axis as a crucial pathway for understanding this condition. In this regard, there is growing interest in therapeutic approaches for ASD through the manipulation of the microbiota, and this project proposes cannabidiol (CBD) as a promising candidate in this context. Previous research has highlighted the antimicrobial potential of CBD, which may select microorganisms known to be beneficial to the CNS. However, the in vivo investigation of how CBD-induced alterations in the microbiome could influence its effects (i.e., its pharmacomicrobiomics) and the pathways through which the selection of gut microbiota may modulate the host's neuroinflammatory profile has not yet been explored. Short-Chain Fatty Acids (SCFAs) emerge as relevant molecules in this context, acting as agonists for GPR109a receptors expressed in various immune cells. In vitro studies have demonstrated that activation of these receptors increases the TREG lymphocyte population, promotes an anti-inflammatory profile in microglia, and attenuates neuroinflammation. Therefore, this study aims to investigate the pharmacomicrobiomics of CBD by analyzing whether one of the ways this compound acts is by altering the pro-inflammatory profile through the selection of SCFA-producing microorganisms, thereby modulating the Immune System in a Valproic Acid-induced animal model of ASD, with the purpose of treating the neuroimmune and behavioral impairments associated with this condition.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

HASSIB, LUCAS; KANASHIRO, ALEXANDRE; PEDRAZZI, JOAO FRANCISCO CORDEIRO; VERCESI, BARBARA FERREIRA; HIGA, SAYURI; ARRUDA, IRIS; SOARES, YAGO; DE SOUZA, ADRIANA DE JESUS; JORDAO, ALCEU AFONSO; GUIMARAES, FRANCISCO SILVEIRA; et al. Should we consider microbiota-based interventions as a novel therapeutic strategy for schizophrenia? A systematic review and meta-analysis. BRAIN, BEHAVIOR, & IMMUNITY - HEALTH, v. 43, p. 15-pg., 2025-02-01. (23/16182-2, 23/16731-6)