Investigating the role of intestinal microbiota in the metabolism of tuberculosis treatment drugs

• Grant number: 25/14886-8
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: March 01, 2026
• End date: February 28, 2027
• Field of knowledge: Biological Sciences - Pharmacology - Clinical Pharmacology
• Principal Investigator: João Paulo Bianchi Ximenez
• Grantee: Cecília Cristina de Souza Rocha
• Supervisor: Michael Zimmermann
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: European Molecular Biology Laboratory, Heidelberg (EMBL), Germany
• Associated to the scholarship: 24/03190-0 - Exploring the Complexities of Neurocryptococcosis: Investigating the Dynamics between Blood-Brain Barrier, Pharmacokinetics, and Inflammation., BP.PD

Abstract

Tuberculosis, an infectious disease caused by the bacillus Mycobacterium tuberculosis, poses a significant global public health challenge. The World Health Organization currently recommends a standardized six-month treatment regimen comprising first-line antituberculosis drugs - rifampicin, isoniazid, ethambutol, and pyrazinamide. The implementation of this therapeutic regimen results in a high treatment success rate, but several factors may contribute to the pharmacokinetic variability observed among patients. The intestinal microbiota plays a fundamental role in maintaining host homeostasis and modulating therapeutic responses across a range of diseases, and It establishes a complex, bidirectional interaction with the host. The intestinal microbiota has the capacity to metabolize a wide range of pharmaceutical compounds, thereby contributing to the modulation of both intestinal and systemic exposure to drugs and their metabolites. The current BEPE proposal aims to investigate, in vitro, the metabolism of first-line antituberculosis drugs by the intestinal microbiota, as well as the potential absorption of the resulting metabolites by the gastrointestinal epithelium. The data and insights generated during the international internship, in conjunction with the expertise developed through the national research project, will contribute to advancing the understanding of host-microorganism interactions in the context of the cellular pharmacokinetics of drugs employed in the treatment of infectious diseases. (AU)