Deciphering the impact of exposures from the the gut microbiome-derived molecular complex in human health and disease

Title Deciphering the impact of exposures from the the gut microbiome-derived molecular complex in human health and disease
Acronym ExpoBiome
Start date 2020-05-01
End date 2025-04-30
Sponsor European Research Council - Consolidator Grant (ERC-CoG)
Institution Luxembourg Centre for Systems Biomedicine
Principal investigator Dr. Paul Wilmes

Project Description

The human gut microbiome is a complex ecosystem, which contributes essential functions to human physiology. Changes to the microbiome are associated with several chronic diseases characterised by inflammation, including neurodegenerative and autoimmune diseases. Microbiome-derived effector molecules comprising nucleic acids, (poly)peptides and metabolites are present at high levels in the gut but have so far eluded systematic study. This gap in knowledge is limiting mechanistic understanding of the microbiome’s functional impact on chronic diseases such as Parkinson’s disease (PD) and rheumatoid arthritis (RA). A combination of advanced high-resolution methodologies will be integrated to comprehensively identify the constituents of this molecular complex and their impact on the human immune system. First, a quantitative, integrated multi-omic analysis will be performed on microbiome samples collected from healthy individuals and patients with newly diagnosed PD or RA. The data will be integrated and analysed using a newly developed knowledge base. Using contextualised prior knowledge (ExpoBiome Map) and machine learning methods, microbial molecules associated with condition-specific immunophenotypes will be identified. Second, the biomarker signature during a model clinical intervention (therapeutic fasting) will be validated and tracked to predict treatment outcomes. Third, microbes and molecules will be screened in personalised HuMiX gut-on-chip models to identify novel anti-inflammatory compounds. By providing mechanistic insights into the molecular basis of human-microbiome interactions, the project will generate essential new knowledge about causal relationships between the gut microbiome and the immune system in health and disease. By facilitating the elucidation of currently unknown microbiome-derived molecules, we will identify new genes, proteins, metabolites and host pathways for the development of future diagnostic and therapeutic applications.