Mechanistic study of gut microbial biotransformation reactions and their physiological role.

Información del proyecto

BiPMeM

Identificador del acuerdo de subvención: 101107447

DOI

10.3030/101107447

Proyecto finalizado el 31 Julio 2024

Fecha de la firma de la CE 15 Marzo 2023

Fecha de inicio 1 Abril 2023

Fecha de finalización 31 Marzo 2025

Financiado con arreglo a

• Marie Skłodowska-Curie Actions (MSCA)

Coste total

Sin datos

Aportación de la UE

€ 173 847,36

Coordinado por

EUROPEAN MOLECULAR BIOLOGY LABORATORY
Germany

Periodic Reporting for period 1 - BiPMeM (Mechanistic study of gut microbial biotransformation reactions and their physiological role.)

Período documentado: 2023-04-01 hasta 2025-03-31

Resumen del contexto y de los objetivos generales del proyecto

The human gut microbiota, the trillions of microbes inhabiting our gastrointestinal tract, encodes an enormous number of metabolic enzymes, responsible for diverse biochemical reactions that determine metabolic microbiota-host interactions. Bacterial biotransformation reactions, the chemical modification of compounds by bacteria, seem to play a central role in such metabolic interplay between the gut microbiota and its human host. A number of gut microbial biotransformations such as reductive and hydrolytic reactions, as well as their metabolic enzymes, have been recently described. However, our mechanistic and physiological understanding remains still limited for many gut microbial biotransformation reactions, such as chemical conjugation. To fill this knowledge gap, this project presents a multidisciplinary plan to systematically investigate conjugative biotransformation reactions of gut bacteria.

Trabajo realizado desde el comienzo del proyecto hasta el final del período abarcado por el informe y los principales resultados hasta la fecha

• Developed a mass spectrometry-based computational pipeline to identify conjugative biotransformation on xenobiotics generated by gut bacteria.
• Successfully identifying gut bacterial enzymes responsible for chemical conjugation by applying high-throughput gut bacterial genetics using gain-of-function library approaches.
• Utilized gnotobiotic mouse models to assess the impact of conjugative enzymes on drug absorption, distribution, metabolism, and excretion (ADME).

Avances que van más allá del estado de la técnica e impacto potencial esperado (incluida la repercusión socioeconómica y las implicaciones sociales más amplias del proyecto hasta la fecha)

This project has significantly expanded our understanding of gut microbiome conjugative biotransformation. The identification of novel bacterial enzymes responsible for chemical conjugation presents potential advancements in personalized medicine, particularly in tailoring drug treatments based on individual microbiome profiles. These findings could lead to the development of predictive models for drug efficacy and safety, offering valuable insights for future research and clinical applications.