NMBU-researcher makes new discoveries concerning gut flora and health

A new study shows that the antibodies in the intestine are tailor-made for the bacteria present there and contribute to stabilising our own personal intestinal flora.

The bacteria we have in the intestines and the immune responses to the bacteria are key to our health. A new model for animal experiments developed at NMBU could be crucial to our understanding of human health in this area.

Continuous adaptation to the bacteria in the environment
We absorb bacteria from our surroundings throughout our entire lives and in order to prevent these from causing disease in the intestines, the body creates antibodies against each and every one of them so that they do not enter the body to create disease but stay in the intestines where, among other things, they help our digestion. The study shows that we maintain a personal composition of these bacteria throughout life.

The study shows how the antibodies in the intestines continuously adapt to new bacteria that we are exposed to whilst also ensuring that the bacteria flora is kept stable.

"The interaction between bacteria and immunity is not only important to each of us as individuals but can also be passed on to the next generation," NMBU-researcher Preben Boysen explained.

Boysen, who is an associate professor at the Department of Food Safety and Infection Biology at NMBU, has contributed to a new study that was published in the renowned publication Nature Immunology recently.

The study shows that the antibodies continuously adapt to the bacteria in the intestines and that the antibodies are produced in different ways depending on whether the bacteria in question are benign or pathogenic.

Such evidence is crucial to our understanding of how the bacteria contribute to our health.

Antibodies against benign intestinal bacteria
The importance of the antibodies in the intestines, called IgA, is known and we know that defects in these antibodies can cause excessive growth of unfavourable bacteria and inflammation in the intestines. Lately it has become clear that antibodies are not only created against infections but also against normal intestinal bacteria. But how the adaptation between antibodies and bacteria is governed has hitherto been unknown. What happens to the composition of antibodies when they come into contact with bacteria through food and the environment if the intestinal microflora is disabled from antibiotics or through infections?

In the study in question, researchers at the universities in Aachen and Hannover in Germany have collaborated with NMBU to demonstrate how substantial changes to the bacterial environment in the intestines of mice and humans affect the variation in antibodies and the cells in which they are produced (Lindner, Thomsen et al. 2015). In order to study this, laboratory mice were examined in many different bacterial environments.

Innovative model developed at NMBU
Mice are the most commonly used laboratory animal in the world. Much of what we know about medicine and human health we have learned from mice. Now, many people have started questioning whether laboratory mice that live hygienic and isolated lives in laboratories are actually a representative animal model for humans, who do not live such protected lives.

"We therefore created a new model to conduct further research concerning this issue. We placed the mice in a pig sty, where the natural living environment of the house mouse, including livestock manure and soil bacteria, was replicated. We then added wild mice, with all the bacteria, parasites, etc. that they carry, together with the laboratory mice for two months," Boysen explained.

This model was used as one of several models to examine the antibody formation in the intestinal mucosa under various environmental conditions. First, the researchers looked at mice that were completely free of bacteria. They had limited antibody variation in the intestines but after intestinal bacteria had been transferred from ordinary laboratory mice, the variation in these antibodies increased. The variation was greatest in the mice used in the NMBU model. The richer a bacterial environment encountered by the mice, the more varied the antibody composition.

"This is a completely new research model, the first of its kind, and can be used for numerous different purposes. After spending time in a natural environment we have created laboratory mice that are different to ordinary laboratory mice. Previously we predominantly studied the mice in very hygienic environments that are nothing like the environments in which people live. We also need to observe them under natural environmental conditions in order to identify crucial correlations," said Boysen.

He believes that the imprinting the mice get in these sties, especially via the intestines, makes it a good model with which to research diseases that affect humans.

The mother's microbiota provides children with a good start in life
Different research has shown that a narrow bacteria composition in the environment can contribute to making children more exposed to allergies. It is especially important for the child to obtain the mother's bacteria through vaginal birth and antibodies from breastfeeding in order to avoid imbalance between the intestinal flora of the child and the immune system.

"We often forget that there are antibodies in breast milk. Breast milk is crucial for passing on immunity. This is one of the reasons why we are mammals. An interesting finding in our study is that the cells that create antibodies which are specially adapted to the mother's intestinal bacteria also travel to the mammary glands. The antibodies are transported to the child's intestines via breast milk and help the newborn baby to stabilise their own personal intestinal bacteria composition. The mother and child live in the same environment and share bacteria and if the antibodies are already carefully adjusted from the start, the child will have a health advantage. Earlier balancing in the baby's intestines can result in calm conditions which in turn can prevent the development of allergies, for example," Boysen explained.

Aiming to research the role of the digestive system in lifestyle disorders
Some research indicates that the emergence of chronic inflammation disorders could be linked to the development of the modern industrial society in which the digestive system is central when it comes to the development of lifestyle disorders.

This subject is also addressed in the popular science book "Darm mit Charme" ("Charming Bowels"), which was recently published in Norwegian, and is an area in which a lot has happened in just the last five years.

"With a greater perspective, we want to use our model to look at typical lifestyle disorders when mice live in a more natural environment with the bacteria that come with such an environment: Do they develop cancer, autoimmune diseases, obesity, cardiovascular disease or allergies to the same extent?" Boysen asked.

Published 24. January 2016 - 15:06 - Updated 23. May 2017 - 19:15