Research

Thesis title: "Modulators of small intestinal barrier dysfunction in nutrition induced metabolic disease and aging."

Thesis outline: As the prevalence of overweight and obesity is still increasing in many countries, the prevalence of related diseases like steatotic liver disease is also increasing. In fact, the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is thought to be around 25% in the general world population. Besides an increased body weight, older age is also a key risk factor in the development of MASLD. Epidemiological studies suggest that by 2030 the number of individuals above the age of 65 years will outnumber these below the age of 5 years. A dysfunction of the intestinal barrier and especially in the small intestine has been discussed to be related to both, the development of MASLD and aging associated changes. In the last decades, dietary habits have changed worldwide. In fact, there has been an uprising prevalence of a vegan diet, being primarily characterized by the consumption of no animal products.
On other notice, the consumption of fructose has increased significantly over the last decades. A high fructose intake is associated with a variety of diseases including MASLD partially through impairment of the intestinal barrier function.

The aim of the project is to determine modulators of nutritional- and aging-related intestinal barrier dysfunction and to determine underlying molecular mechanisms. To investigate the effect of an isocaloric switch of healthy subjects to a vegan or omnivorous diet, respectively following the DACH nutrient intake recommendations, a randomized cross-over design study will be performed. The determination of metabolites in stool samples will be assessed. Furthermore the measurement of the effect of the intervention on the gut microbiota via DNA-sequencing and metaproteomic analyses from stool will be performed. Also the expression of different inflammation parameters will be assessed.
To investigate the effect of fructose on the intestinal barrier, in-vitro and ex-vivo experiments will be conducted treating the model organisms with fructose ± metformin. Markers of intestinal permeability will be determined.
Samples of an animal model will be analyzed and in-vitro experiments will be conducted regarding the relation between aging and intestinal barrier dysfunction. Markers of intestinal permeability will be determined.
To simulate the process of digestion an ex-vivo digestion model will be established.

Supervisors: Ina Bergheim, Elke Heiß

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