Constraint-based modelling of host-microbe co-metabolism: Bridging in silico microbial and human drug transformation pathways
Martinelli, Filippo
Martinelli, Filippo
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Publication Date
2024-09-26
Type
doctoral thesis
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Abstract
This thesis aims to address the critical gap in understanding the intricate metabolic interplay between host and microbial symbionts. Through the utilization of constraint-based modelling, which relies on manually curated and validated organism-specific reconstructions converted into mathematical models, this research aims to bridge in silico representations of microbial and human drug metabolic networks. By doing so, it lays the groundwork for future studies aimed at guiding the design of tailored therapeutic interventions. Chapter 1 presents a submitted review encompassing the current knowledge regarding drug microbial metabolism. Chapter 2 introduces a protocol paper delineating the precise steps required to accurately map human drug metabolism within a comprehensive whole-body model. Chapter 3, a published paper, delves into the evaluation of host-microbiota co-metabolism in the production of formate in urine, serving as a proof of concept on how host-microbiome co-metabolism can be assessed for a specific metabolic pathway. Chapter 4 reports the initial findings of a preliminary investigation into drug microbial metabolizing capacities across two distinct healthy cohorts, offering a glimpse into the variability of microbial metabolism in different populations. The conclusions chapter offers a forward-looking perspective on the future applications of personalised host-microbiome models integrated with drug metabolism.
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University of Galway
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Attribution-NonCommercial-NoDerivatives 4.0 International