Title of project

Gut Barrier Integrity as the defining factor for obesity-associated systemic inflammation

Abstract

Obesity is a major global health challenge, driving chronic low-grade inflammation that
contributes to conditions such as type 2 diabetes, cardiovascular disease, liver disease, and
neurodegenerative disorders. Increasing evidence suggests that impaired gut barrier function
allows bacteria and bacterial products to enter the circulation, triggering systemic
inflammation. Diets high in fat and ultra-processed foods, combined with a sedentary lifestyle,
appear to weaken gut barrier integrity, potentially worsening obesity-related complications.

This project brings together experts in clinical, basic, and translational research to investigate
how gut barrier dysfunction contributes to obesity-associated inflammation. Our objectives are
to: i) assess how excessive nutrient intake from a high-fat, ultra-processed diet combined with
a sedentary lifestyle impairs gut barrier function, ii) elucidate the causal role of gut-barrier
dysfunction in systemic inflammation, iii) determine the role of the gut microbiota in changes
observed after overfeeding, and iv) characterise regional gut permeability using biopsies
collected in humans after intake of a high-fat, ultra-processed diet.

Using a retro-translational approach, we will combine human trials with advanced rodent
models. Molecular analyses will explore how diet, microbes, and host immunity interact to
influence gut barrier integrity and inflammatory responses. Preliminary findings from our
group indicate that a short-term hypercaloric diet alters gut barrier markers in healthy
individuals, and that these changes are reversible upon return to a normocaloric diet. In this
This PhD project aims to clarify how gut barrier dysfunction drives obesity-associated systemic
inflammation and to identify potential therapeutic targets to reduce obesity-related disease.