When laboratory mice are given a gut flora similar to that of wild mice, their intestinal barrier becomes stronger and the risk of colitis is reduced, especially when combined with dietary fiber. This is shown in the doctoral research of Signe Birkeland, who investigates how environment and diet influence the development of inflammatory diseases in the gut.
The doctoral work of Signe Birkeland shows that a natural gut flora in laboratory mice alters the intestinal barrier and protects against colitis, especially combined with dietary fiber.
Below, she answers four questions about her research:
Why is this research important?
We are seeing a global increase in non-communicable diseases (including lifestyle associated diseases), several of which are linked to the digestive system. These are influenced by both genetics, diet, and other lifestyle factors, and several hypotheses trying to explain the increase in “modern” diseases revolve around a lack of sufficient microbial exposure. The consequence of this is that the gut flora of people in modern and urban societies has adapted to the modern lifestyle in a way that is potentially unfavorable to our health.
Another challenge is that discoveries made in laboratory mice cannot always be reproduced in humans. Laboratory mice are among our most important model organisms to understand human physiology. In line with the disturbances we see in the human gut flora, there are also various hypotheses that today's laboratory mice are “too clean”. The hygienic housing of lab mice is in stark contrast to how, for example, wild mice live. “Naturalization models” therefore attempt to introduce laboratory mice to a more natural environment, where they are exposed to microbes that can establish themselves in their intestines and potentially affect the intestinal barrier, immune defense and thus also the risk of developing various diseases.
What were the goals of you phd-work?
The goals of this work were to explore how a natural gut flora in laboratory mice affects the intestinal barrier and disease outcomes in an animal model of colitis (large intestinal inflammation), and how this could be affected by different dietary fibers in the diet.
What are your most important results?
We employed various methods to provide laboratory mice with a “natural” gut flora, which means that we aim to recreate a flora that is expected to be found in wild mice and to which they are better adapted to through evolution. We did this by housing laboratory mice in a farmyard-like environment, mimicking where wild house mice normally live. We also co-housed laboratory mice together with wild house mice to transfer microorganisms from wild mice to laboratory mice. This way, “clean” laboratory mice are exposed to different microorganisms than they are in the laboratory, contributing to a more “natural” gut flora.
We found that a natural gut flora in laboratory mice affects the intestinal mucosa (the intestinal barrier) and protects against colonic inflammation, especially in combination with dietary fiber. “Clean” laboratory mice, on the other hand, showed a higher degree of inflammation, especially those that were fed a high dose of dietary fibers. This seemed to be related to which bacteria in the gut made use of the dietary fiber, as the laboratory mice showed an increase in several bacterial genera that have previously been linked to worsened symptoms in this disease model. These bacteria may thus have been outcompeted by the “natural” bacteria, which we have also seen to provide a more activated intestinal barrier and thus protect against inflammation. This protection was also replicated in mice that received fecal transfers from mice with a "natural" gut flora, further supporting the role of the gut flora in influencing the risk of developing inflammatory diseases in the gut.
What is the potential impact of your research:
This research contributes to an increased understanding of the interaction between the gut flora and the host (laboratory mice) and how the diet, specifically dietary fiber, contributes to these interactions.
Fact box:
Signe Birkeland
- Has previously studied: Bachelor and Master in biotechnology (molecular biology) ved KBM (NMBU)
- Is from: Lier, Norway
- Has now completed her PhD at NMBUs Faculty for Chemistry, Biotechnology and Food Science
- The title of her thesis in English and Norwegian:
- Gut microbiome in naturalized mice: Effects on intestinal barrier, dietary fibers, and gut inflammation
- Tarmmikrobiomet i naturaliserte mus: effekter på tarmbarrierefunksjon, kostfiber og tarmbetennelse
- Main supervisor: Harald Carlsen
- Co-supervisors: Preben Boysen, Henriette Markov Arnesen, Bjørge Westereng