PhD defence by Julius Emil Brinck

Principal supervisor:

• Professor Tine Rask Licht

Co-supervisors:

• Associate Professor Anurag Kumar Sinha
• Associate Professor Martin Frederik Laursen

Examiners:

• Associate Professor Mikkel Bentzon-Tilia, DTU Bioengineering
• Professor Dennis Sandris Nielsen, University of Copenhagen
• Professor Yolanda Sanz Herranz, Institute of Agrochemistry and Food Technology

Chairperson at defence:

• Professor Egon Bech Hansen

Resume
The human gut microbiota, consisting of trillions of microorganisms present in the gastrointestinal tract, impacts health through the production of a variety of metabolites produced during microbial metabolism. These molecules act as signaling molecules that affect human physiology. However, strategies to modify gut microbial metabolite production, such as through dietary interventions, often yield inconsistent effects, with high variability between individuals. A major limitation of many gut microbiome studies is that the effects of inherent gastrointestinal environmental conditions, such as pH, transit time and nutrient availability, are rarely addressed.

This PhD thesis investigates how these environmental physical and chemical factors influence gut microbiota composition and metabolism, focusing on the aromatic amino acid-derived metabolites. The findings show that microbial metabolic output is driven by changes in gene expression and metabolic activity in response to pH and substrate availability, rather than just alterations in microbial abundance and composition.

Two key regulatory mechanisms of gut microbial metabolism of the aromatic amino acid tryptophan are presented. First, a mildly acidic intestinal pH inhibits microbial production of indole, a metabolite derived from tryptophan and a precursor to indoxyl sulfate, which has been associated with chronic kidney disease and atherosclerosis. Second, the presence of carbohydrates in the gut lowers indole production and shifts tryptophan metabolism toward the formation of other health-promoting metabolites. The study also shows that intestinal pH can affect the production of tyramine, a metabolite frequently associated with harmful health effects, derived from the aromatic amino acid tyrosine, by influencing gene expression and the abundance of the bacterial producer species.

These findings highlight the importance of the gastrointestinal tract’s physical and chemical environment in shaping microbial metabolism. Understanding and modulating these factors may pave the way for the development of more effective, personalized dietary and therapeutic strategies to improve microbiome-mediated health outcomes.

A copy of the PhD thesis is available for reading at the department.