Periodic Reporting for period 1 - BiomeDxRx (Microbiome-based diagnostics and therapeutics)
Periodo di rendicontazione: 2023-10-01 al 2025-03-31
In recent years, the human microbiome has emerged as a key modulator of health and disease, yet translating this knowledge into actionable therapeutics remained limited by a lack of scalable, data-driven platforms. Building on discoveries from our ERC-funded project, we identified specific microbial genes, pathways, and strains associated with cardiometabolic conditions using a deeply phenotyped human cohort of over 10,000 individuals. Our metagenome-wide association studies revealed tens of thousands of significant associations between microbial genetic variants and host traits such as BMI, blood pressure, and glucose metabolism, often with surprisingly large effect sizes. These findings enabled us to prioritize bacterial strains most strongly linked to disease phenotypes for downstream diagnostic and therapeutic applications.
In this ERC-PoC project, we translated our computational discoveries into tangible therapeutic assets. Leveraging our unique access to participants from the original cohort, we recontacted individuals harboring the most promising strains, isolated and functionally characterized them, and established a biobank of candidate therapeutic bacteria. We then signed licensing deals with industry partners to grow these strains and evaluate their efficacy in clinical trials targeting obesity and other cardiometabolic disorders. This closed-loop pipeline—spanning large-scale human data, novel analytics, and strain isolation—is both scalable and disease-agnostic, providing a transformative platform for the development of microbiome-based diagnostics and therapeutics. Through this work, we directly address the global burden of metabolic disease and set the stage for microbiome interventions with real-world impact.
In this ERC-PoC project, we translated our computational discoveries into tangible therapeutic assets. Leveraging our unique access to participants from the original cohort, we recontacted individuals harboring the most promising strains, isolated and functionally characterized them, and established a biobank of candidate therapeutic bacteria. We then signed licensing deals with industry partners to grow these strains and evaluate their efficacy in clinical trials targeting obesity and other cardiometabolic disorders. This closed-loop pipeline—spanning large-scale human data, novel analytics, and strain isolation—is both scalable and disease-agnostic, providing a transformative platform for the development of microbiome-based diagnostics and therapeutics. Through this work, we directly address the global burden of metabolic disease and set the stage for microbiome interventions with real-world impact.
The activities performed in this ERC-PoC project were fully aligned with our proposed plan and built directly upon the foundational discoveries of our ERC-funded research. We began by extending our computational analyses to prioritize bacterial strains most strongly associated with cardiometabolic traits. Leveraging metagenomic and SNP-level resolution from our large-scale cohort, we refined our selection of candidate strains by integrating additional phenotype-microbiome associations and cross-validating mechanistic links between bacterial functions and host outcomes.
Following this, we moved into the technically challenging phase of isolating these strains from participants in our cohort. This effort involved recontacting individuals identified as harboring specific bacterial strains and establishing a custom culturomics pipeline to support the growth of anaerobic gut bacteria—an inherently delicate and complex process. Despite initial growth difficulties, particularly with strains requiring highly specific co-factors or synergistic microbial partners, we successfully isolated several of the prioritized strains. Metabolomic characterization of these isolates further validated their therapeutic relevance and mechanistic potential.
The primary outcomes of the project are twofold: first, the establishment of a curated strain biobank containing functionally characterized bacteria associated with key metabolic traits; and second, the execution of licensing agreements with commercial partners. These deals mark a critical milestone, as they commit to scaling and testing the selected strains in clinical trials targeting obesity and related cardiometabolic diseases. Our work not only validated the technical feasibility of the proposed pipeline—from data-driven discovery to therapeutic strain isolation—but also laid the groundwork for real-world deployment of microbiome-based interventions.
Following this, we moved into the technically challenging phase of isolating these strains from participants in our cohort. This effort involved recontacting individuals identified as harboring specific bacterial strains and establishing a custom culturomics pipeline to support the growth of anaerobic gut bacteria—an inherently delicate and complex process. Despite initial growth difficulties, particularly with strains requiring highly specific co-factors or synergistic microbial partners, we successfully isolated several of the prioritized strains. Metabolomic characterization of these isolates further validated their therapeutic relevance and mechanistic potential.
The primary outcomes of the project are twofold: first, the establishment of a curated strain biobank containing functionally characterized bacteria associated with key metabolic traits; and second, the execution of licensing agreements with commercial partners. These deals mark a critical milestone, as they commit to scaling and testing the selected strains in clinical trials targeting obesity and related cardiometabolic diseases. Our work not only validated the technical feasibility of the proposed pipeline—from data-driven discovery to therapeutic strain isolation—but also laid the groundwork for real-world deployment of microbiome-based interventions.
Our project has produced results that significantly advance the state of the art in microbiome-based therapeutic development. Traditionally, discovery pipelines for such interventions rely on preclinical animal models or hypothesis-driven selection of microbial species. In contrast, we developed and demonstrated a fully human, data-driven discovery-to-isolation pipeline that begins with large-scale, high-resolution metagenomic data from a deeply phenotyped cohort and ends with the isolation and characterization of therapeutically relevant bacterial strains. This approach offers not only increased biological relevance and predictive power but also greater scalability and adaptability across multiple disease domains.
The key breakthroughs achieved include the identification of novel, strain-level bacterial associations with cardiometabolic traits; the successful isolation of prioritized strains from human donors despite considerable technical challenges; and the formation of licensing partnerships with commercial entities for clinical testing. These outcomes validate our platform as a robust, end-to-end solution for microbiome therapeutic discovery and provide a template that can be replicated across additional disease areas. The strains isolated in this project have entered the commercialization pipeline and will be evaluated in human clinical trials targeting obesity and metabolic dysfunction—an essential next step in demonstrating efficacy and therapeutic potential.
To ensure further uptake and long-term success, continued research will be needed to expand the catalog of disease-associated strains and to deepen our understanding of their mechanisms of action. Demonstration projects and early clinical trials will be critical for de-risking these interventions and attracting additional commercial investment. Additional needs include: IPR support to protect strain-level discoveries and diagnostic algorithms; regulatory engagement to ensure alignment with evolving microbiome-based therapeutic frameworks; and financial access to scale biomanufacturing and downstream clinical development. Overall, our results provide both proof-of-concept and a strong foundation for scaling human-centered microbiome therapeutics into mainstream medicine.
The key breakthroughs achieved include the identification of novel, strain-level bacterial associations with cardiometabolic traits; the successful isolation of prioritized strains from human donors despite considerable technical challenges; and the formation of licensing partnerships with commercial entities for clinical testing. These outcomes validate our platform as a robust, end-to-end solution for microbiome therapeutic discovery and provide a template that can be replicated across additional disease areas. The strains isolated in this project have entered the commercialization pipeline and will be evaluated in human clinical trials targeting obesity and metabolic dysfunction—an essential next step in demonstrating efficacy and therapeutic potential.
To ensure further uptake and long-term success, continued research will be needed to expand the catalog of disease-associated strains and to deepen our understanding of their mechanisms of action. Demonstration projects and early clinical trials will be critical for de-risking these interventions and attracting additional commercial investment. Additional needs include: IPR support to protect strain-level discoveries and diagnostic algorithms; regulatory engagement to ensure alignment with evolving microbiome-based therapeutic frameworks; and financial access to scale biomanufacturing and downstream clinical development. Overall, our results provide both proof-of-concept and a strong foundation for scaling human-centered microbiome therapeutics into mainstream medicine.