ASSOCIATION OF GUT MICROBIOTA WITH THE DIABETIC PHENOTYPE OF GOTO-KAKIZAKI RAT (A NON-OBESE DIABETIC MODEL)

• Grant number: 23/14878-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: July 02, 2024
• End date: January 01, 2025
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Rui Curi
• Grantee: Gabriela Mandu Gimenes
• Supervisor: Keith Alexander Sharkey
• Host Institution: Centro de Ciências Biológicas e da Saúde. Universidade Cruzeiro do Sul (UNICSUL). São Paulo , SP, Brazil
• Institution abroad: University of Calgary, Canada
• Associated to the scholarship: 22/11249-9 - Slow intestinal transit and intestinal microbiota composition in the genesis of insulin resistance in Goto-Kakizaki rats, BP.DD

Abstract

Professor Keith A. Sharkey is one of the most globally recognized scientists in intestinal microbiota research. During the BEPE, Gabriela will carry out experiment on the relevance of intestinal microbiota in the diabetic phenotype of Goto-Kakizaki (GK) rats. The GK rat develops type 2 diabetes mellitus (T2DM) spontaneously, without obesity. T2DM causes marked changes in enteric nervous system (ENS) activity and the whole intestine functioning. Our group reported slow intestinal transit, increased pro-inflammatory markers, and differences in small intestine inhibitory nitrergic neurons in the myenteric plexus of 16-week-old GK compared to Wistar rats. Constipation may play an important role in triggering insulin resistance (IR) in these animals by altering the composition of the microbiota. The involvement of the intestinal microbiota in establishing diabetic condition and low intestinal transit will be investigated through gut microbiota depletion induced by an antibiotic cocktail. Quantification of bacterial load, peripheral insulin sensitivity, intestinal motility, and myenteric plexus cells will be studied to examine the relevance of the intestinal microbiota in the genesis of the diabetic phenotype of GK rats. The hypothesis is that the lower intestinal transit (constipation) leads to IR and T2DM, without obesity, by promoting marked changes in the intestinal microbiota composition. Due to his broad knowledge in the field, Professor Sharkey will markedly contribute to Gabriela's thesis, guiding her in interpreting the results already obtained and designing complementary experiments. Gabriela already presented the results obtained to Professor Sharkey and Dr. Minh Dang Nguyen through an online meeting. Gabriela will present her updated results to Professor Sharkey's group upon her arrival in July of next year.