Comparison of the hepatic proteomic profile between male and female germ-free mice transfected with human gut microbiota and exposed to low doses of fluoride

• Grant number: 24/22598-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2025
• End date: May 31, 2026
• Field of knowledge: Health Sciences - Dentistry - Social and Preventive Dentistry
• Principal Investigator: Marília Afonso Rabelo Buzalaf
• Grantee: Kauan Cristiano de Souza
• Host Institution: Faculdade de Odontologia de Bauru (FOB). Universidade de São Paulo (USP). Bauru , SP, Brazil

Abstract

Fluoride (F) is widely used in public health due to its benefits in preventing dental caries but also presents toxicity when consumed in excess, causing metabolic and cellular alterations as well as fluorosis. Recent studies have highlighted sex-related differences in responses to fluoride, linked to metabolic factors. A relevant aspect of this research is the relationship between fluoride and propionic acid, a short-chain fatty acid essential in the citric acid cycle (CAC) and in the modulation of secretory autophagy. Alterations in propionic acid levels can overload the CAC, impairing the production of reducing equivalents critical for the respiratory chain and leading to metabolic imbalances in the liver. Previous studies have shown that both the serum concentration of propionic acid and the severity of dental fluorosis were modulated by sex, emphasizing the importance of investigating the associated mechanisms. Understanding these variations is crucial for identifying the underlying mechanisms of fluoride toxicity and its impacts on human health. Thus, the present project aims to compare the hepatic proteomic profile between male and female germ-free mice transplanted with human gut microbiota and exposed to low doses of fluoride. For this purpose, germ-free C57BL6/J mice were transplanted with human intestinal microbiota and divided into groups based on sex and exposure to different fluoride concentrations in drinking water (0 and 10 mg/L). The treatment lasted five weeks, after which the animals were euthanized, and their livers were collected, cleaned, and stored for proteomic analysis. Following the acquisition of proteomic data, analysis and interpretation will be performed using bioinformatics tools. Protein expression will be compared between groups using statistical tests (p<0.05). This study employs advanced proteomics methods to explore the impacts of fluoride on liver metabolism, providing potential insights into the interaction between sex, fluoride, and energy metabolism. These findings may contribute to the development of safer strategies for fluoride use in public health and a deeper understanding of gender differences in responses to chemical agents.