Influence of Gestational Dysbiosis on Histone Acetylation Profile in the Intestinal Epithelium of Offspring in a Murine Mode

• Grant number: 25/13462-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2025
• End date: June 30, 2026
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Valquiria Aparecida Matheus
• Grantee: Maria Fernanda Rizzo de Araujo Pereira
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Inflammatory Bowel Diseases (IBD), such as Crohn's disease and ulcerative colitis, are chronic and debilitating conditions that affect millions of people worldwide, significantly impacting quality of life and public health. The increasing prevalence of these diseases poses a major challenge and is associated with imbalances in the gut microbiota (dysbiosis) and epigenetic modifications, such as histone acetylation, mainly mediated by short-chain fatty acids (SCFAs), including acetate, butyrate, and propionate. Dysbiosis during pregnancy can compromise the composition of the maternal microbiota and the production of SCFAs, essential metabolites for regulating physiological processes and for the proper development of the fetal immune, nervous, and gastrointestinal systems.This research proposes to analyze the histone acetylation profile in offspring from mothers with gestational dysbiosis induced by antibiotics, correlating these epigenetic changes with susceptibility to experimental colitis. In addition, the efficacy of sodium butyrate supplementation during pregnancy will be investigated as a potential therapeutic strategy to restore microbial balance and prevent the development of IBD in the offspring.The study will be conducted using C57BL/6J mice, divided into four experimental groups: antibiotic-induced dysbiosis (ABX), sodium butyrate supplementation (Butyrate), combined dysbiosis and supplementation (ABX + Butyrate), and a control group. After weaning, the offspring will undergo induction of colitis with dextran sulfate sodium (DSS) and will be evaluated for epigenetic (histone acetylation), immunological, behavioral, and histopathological changes in the colon.This study aims to deepen the understanding of the effects of gestational dysbiosis on intestinal health and the epigenetic programming of the offspring, contributing new insights into therapeutic strategies for the prevention and treatment of inflammatory bowel diseases, whose incidence has increased significantly in contemporary society.