PhD defence by Chrysoula Dimompoulou

Principal supervisor:

• Professor Tine Rask Licht

Co-supervisor:

• Martin Iain Bahl

Examiners:

• Assoc. Professor Mikael Lenz Strube, Department DTU
• Professor Karen Angeliki Krogfelt, Rosklide University
• Research PM Ruben Vasquez Uribe, VIB-KU Leuven

Chairperson at defence:

• Assoc. Professor Mikael Lenz Strube

Resume

The gut microbiota plays a pivotal role in maintaining a healthy body, influencing our well-being through the metabolites they generate. Traditionally, probiotics have been used to shape a healthier microbiome. However, recent advances in synthetic biology have opened new opportunities, including the development of gene-edited probiotic strains. Combination of our knowledge on the microbiome metabolites and such technologies, can lead to new strains that can selectively enhance the production of natural gut bacterial metabolites.

In this work, the prominent probiotic strain Escherichia coli Nissle 1917 (EcN) was engineered to produce indole lactic acid (ILA), a tryptophan gut bacterial metabolite. When administered to mice, this engineered strain, EcN aldh, significantly increased ILA levels in the intestine and the systemic circulation of the animals. As ILA is known for its anti-inflammatory properties, EcN aldh was further tested in a murine model of colitis. The results demonstrated that the strain had a positive impact on the initial recovery phase of the inflamed intestinal tissue. Furthermore, our analysis revealed several host pathways that were beneficially affected by the ILA-producing EcN.

As a result, EcN aldh holds promise as a potential aid in recovery from conditions associated with intestinal inflammation, such as inflammatory bowel disorders. This application could be particularly valuable for individuals with chronic conditions, especially considering the low natural levels of ILA in the intestines of adults, which can be further depleted by certain modern diets.