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Decoding the role of dietary xenobiotic-active CAZymes in Ruminococcus gnavus: mechanisms, microbiome interactions, and health implications

Project description

Bacterial processing of dietary compounds

The gut microbiome plays a fundamental role in human health, and diet is one of its most powerful modulators. Beyond breaking down dietary fibres, gut bacteria also process bioactive dietary compounds, including xenobiotics, plant pigments, flavonoids and other small molecules. However, the implicated enzymes in this breakdown and their health implications remain largely unknown. With the support of the Marie Skłodowska-Curie Actions programme, the XENOZYME project investigates novel enzymes in the gut bacterium Ruminococcus gnavus that process these dietary compounds, releasing metabolites that influence gut barrier function and immune responses. Using multi-omics, structural biology and advanced models, researchers will characterise these enzymes and assess their role in microbiome variability and inflammatory bowel disease. This work is expected to uncover new biomarkers and potential therapeutic targets.

Objective

The human gut microbiota plays a central role in health and disease, with diet being one of its strongest modulators. While much is known about the microbial enzymes that degrade diet polysaccharides in the human gut, the metabolism of dietary xenobiotics (XB), small bioactive compounds often glycosylated, are poorly understood. Dietary XB deglycosylation by gut bacteria releases metabolites that can influence microbial ecology and host physiology, yet the enzymes driving these transformations are largely unknown. This project will investigate novel XB-active carbohydrate-active enzymes (XB-CAZymes) in the human gut symbiont Ruminococcus gnavus, a strain-diverse species prevalent across populations and strongly associated with inflammatory bowel disease. Through multi-omics, recombinant enzyme production, enzymatic assays, and structural biology, XB-CAZymes will be identified and their mechanisms of action characterised. Functional validation will be carried out using R. gnavus knockout mutants, while advanced in vitro models of the human gut will assess how XB metabolites affect gut barrier integrity and immune responses. R. gnavus isolation and multi-omics analyses of human faecal samples from an existing elderly cohort will provide ecological and interindividual perspectives, linking enzyme function to microbiome variability and health implications. The project will generate fundamental knowledge to refine CAZy classification, uncover biomarkers and therapeutic targets, and identify enzymes with biotechnological potential. Beyond scientific advances, the fellowship will provide the researcher with first-hand expertise in cutting-edge integrative microbiome science, preparing them to lead interdisciplinary research at the interface of diet, microbiota, and health in Europe and internationally.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

(opens in new window) HORIZON-MSCA-2025-PF

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Coordinator

QUADRAM INSTITUTE BIOSCIENCE
Net EU contribution
€ 260 347,92
Address
QUADRAM INSTITUTE BIOSCIENCE NORWICH RESEARCH PARK
NR4 7UQ NORWICH
United Kingdom
Region
East of England East Anglia Breckland and South Norfolk
Activity type
Research Organisations
Links
Total cost
No data