Digital microbe database unlocks patient response to treatment

Scientists at the University of Galway, in collaboration with APC Microbiome Ireland, a world-class SFI Research Centre, have developed a database of over 7,000 digital microbes, allowing computer simulations of how drug treatments operate and how patients may respond.

Digital microbe database unlocks patient response to treatment
l-r: Filippo Martinelli and Bram Nap, both PhD students at the University of Galway Molecular Systems Physiology group; Professor Ines Thiele Professor of Systems Biomedicine, and Dr Ronan Fleming, Associate Professor in Medicine at the University of Galway. Image Credit: University of Galway.

The resource is a defining moment in the scientific understanding of human response to medical treatment because it enables computer simulations and predictions of differences in metabolism between individuals, including for diseases like Parkinson’s disease, inflammatory bowel disease, and colorectal cancer.

The database, known as AGORA2, expands on the insights gained in the creation of the first digital microbe resource, AGORA1. AGORA2 contains 7,203 digital microbes that were created using experimental knowledge from scientific publications, with a specific focus on drug metabolism.

A group of researchers from the University of Galway’s Molecular Systems Physiology group, guided by APC Microbiome Ireland Principal Investigator Professor Ines Thiele, developed the resource.

Using computational modeling, the team’s research aims to improve precision medicine.

AGORA2 is a milestone towards personalized, predictive computer simulations enabling the analysis of person-microbiome-drug interactions for precision medicine applications. Humans are hosting a myriad of microbes. Just like us, these microbes eat and interact with their environment. Considering that we are all unique, each of us hosting an individual microbiome our metabolism is also expected to vary between individuals.”

Ines Thiele, Professor, University of Galway

The insight provided by the database of digital microbes presents a healthcare opportunity to harness individual differences in metabolism to provide personalized, improved treatments in ‘precision medicine’, compared to a currently more general ‘one-size-fits-all’ approach,” adds Professor Thiele.

Professor Thiele elaborates, “Besides our food, our individual microbiomes also metabolize the medicines we take. The same drug may therefore manifest diverse effects in disparate people because of the differences in metabolism performed by the different microbiomes.”

By using digital microbe resource AGORA2, computer simulations revealed that drug metabolism differs significantly between individuals, owing to differences in their microbiomes.

The AGORA2-based computer simulations were distinct in that they allowed the identification of microbes and metabolic processes for individual drugs that were correlated with clinical observations.

The study was published in the journal Nature Biotechnology.

The researchers at the University of Galway illustrated that AGORA2 facilitates customized, strain-resolved modeling by predicting the drug conversion potential of gut microbiomes from 616 colorectal cancer patients and controls, which differed significantly between people and directly linked with age, sex, body mass index, and disease stage.

This implies that the group will be able to create digital representations and predictions for the divergent microbes.

Knowledge of our individual microbiomes and their drug metabolizing capabilities represents a precision medicine opportunity to tailor drug treatments to an individual to maximize health benefit while minimizing side effects. By using AGORA2 in computer simulations our team have showed that the resulting metabolic predictions enabled superior performance compared to what was possible to date.”

Ines Thiele, Professor, University of Galway

This research is a perfect illustration of the power of computational approaches to enhance our understanding of the role of microbes in health and disease—significantly this digital platform will be a fantastic resource that could lead to the development of novel personalized therapeutic approaches which take the microbiome into account,” added Professor Paul Ross, Director of APC Microbiome Ireland.

Source:
Journal reference:

Heinken, A., et al. (2023) Genome-scale metabolic reconstruction of 7,302 human microorganisms for personalized medicine. Nature Biotechnology. doi.org/10.1038/s41587-022-01628-0.

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