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Diet-driven evolution in a human gut commensal bacterium: impact on niche adaptation and host physiology

Project description

How diet impacts host-microbiota interactions and human health

Changes in gut microbiota composition and function are associated with increased severity of metabolic disorders and infectious diseases. A diet that is low in fibre and high in fat and simple sugars alters the microbiota, reduces bacterial diversity, and increases host susceptibility to inflammation and infection. Studies show that this diet can select for specific mutations in the gut commensal Bacteroides thetaiotaomicron that may influence the degradation of mucin-derived glycans and adaptation to the intestinal niche. The EU-funded EvoBacNiche project will generate B. theta mutants carrying diet-selected mutations and investigate their ability to degrade mucin-derived glycans, colonise intestinal niches, and affect host susceptibility to inflammation and infection in experimental models. The project’s goal is to identify the molecular mechanisms linking diet, microbiota evolution, and host health.

Objective

Gut microbiota perturbations are associated with increased severity of human pathologies including metabolic disorders and infectious diseases. Diet influences host physiology in a microbiota-dependent manner. In mice, a diet low in fiber and high in fat and simple sugars (western diet: WD) lowers bacterial diversity, alters microbiota functions, and increases host susceptibility to infection and inflammation. This susceptibility is associated with decreased mucus layer thickness that presumably depends on the activity of mucus-degrading species. Within-host evolution experiments show WD-dependent selection of mutations targeting degradative pathways of mucin-derived glycans in the intestinal commensal Bacteroides thetaiotaomicron (B.theta). Mutations targeting an uncharacterized starch utilization-like system gene showed the strongest frequency fluctuations between standard and western diet. However, the functional consequences of these mutations remain uncharacterized. We hypothesize that WD-selected mutations contribute to spatial niche acquisition, reduction of mucus layer thickness, and increased host susceptibility to pathogen infections. To address this, I will construct isogenic B.theta mutants carrying diet-selected mutations. The mutants will be tested for their ability to degrade mucin-derived glycans in vitro, in a gut-on-chip and in animal models. Their initial spatial distribution will be monitored in mice with a conventional microbiota fed either a standard or western diet. Long-term niche establishment along the gastrointestinal tract and near the mucosal surface, and host susceptibility to inflammation and Citrobacter rodentium infection, will be evaluated in gnotobiotic mice within a community of human-associated bacteria under the two dietary regimens. This study thereby aims to identify molecular mechanisms by which diet impacts host-microbiota interactions at the mucosal surface and to assess their effects on host health and disease.

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-WIDERA-2025-TALENTS-01

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Coordinator

FUNDACAO GIMM - GULBENKIAN INSTITUTE FOR MOLECULAR MEDICINE
Net EU contribution
€ 191 343,12
Address
AVENIDA PROFESSOR EGAS MONIZ
1649-035 LISBOA
Portugal
Activity type
Research Organisations
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Total cost
No data

Partners (1)