PhD defence by Anna Pii Hjørne

Principal supervisor:

• Professor Tine Rask Licht

Co-supervisor:

• Associate Professor Martin Frederik Laursen

Examiners:

• Senior researcher Louise Ramhøj, DTU Food
• Professor Jens Walter, UCC, Ireland
• Associate Professor Camilla Hartmann Friis, UCPH

Chairperson at defence:

• Professor Egon Bech Hansen

Resume
Our gut is home to trillions of microbes, known as the gut microbiota, that help break down food and produce substances that affect our health. Some of these substances, such as short-chain fatty acids (SCFAs) derived from the fermentation of fiber, are beneficial to health. Others, such as p-cresol sulfate and indoxyl sulfate, are associated with negative health effects and are formed when proteins are broken down. This thesis examines how the speed at which food passes through the gut, known as intestinal transit time (TT), influences the balance between these beneficial and detrimental microbial products. Using mice as a model, we slowed down TT with a drug called Imolope® and studied how a slowed TT, combined with dietary fiber interventions, affected the composition and activity of the gut microbiota.

We found that slowing the TT altered the gut microbiota composition, including an increase in a specific bacterium that can break down the gut’s protective mucus layer. Slower TT also resulted in a lower production of beneficial SCFAs, occurring earlier in the intestine when the diet was low in fermentable fiber. Interestingly, not all fibers had the same effect: fermentable fibers supported SCFA production, while cellulose did not have the same effect. Surprisingly, slowing TT also triggered a rise in the gut hormones GLP-1 and PYY, which help regulate appetite and blood sugar. This suggests that the body responds to slowed TT in complex ways beyond just changes in the microbiome. Finally, we tested whether the microbiome itself could influence TT by transferring gut microbes from humans and mice into germ-free mice (mice that lack microbes). While the presence of microbes accelerated TT, the TT variation between the donors was not transferred, indicating that gut microbiome composition alone does not explain why some people have a slower TT than others.

In short, this research highlights the importance of considering the speed at which food passes through the gut in microbiome and gut health research, while also opening the door to more personalized nutritional strategies tailored to individual differences in digestive transit.

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