Multiple Sclerosis: does the colon affect the immune system?

Interview with Prof Hartmut Wekerle, Director Emeritus, Max Planck Institute of Neurobiology, Martinsried

Multiple sclerosis apparently can strike anyone - regardless of age, family history, lifestyle or gender. Yet why then does it not strike everyone? Genetic and environmental factors appear not to be the only reason whether it develops or not. The countless microorganisms that colonize our intestinal tract could also be involved in this.


Photo: elderly man with glasses and white hair

Prof. Hartmut Wekerle; ©MPI für Neurobiologie/ R. Schorner

In this interview with, Prof Hartmut Wekerle talks about the impact of the microbiome, our gut microbiota on the immune system and how changes here might cause autoimmune diseases such as multiple sclerosis (MS).

Prof Wekerle, what role does the human microbiome play in triggering MS?

Prof Hartmut Wekerle: We originally noticed in animal models that a normal gut microbiota is also responsible for triggering autoimmune brain disease.

What is the relationship between gut microbiota and the immune system?

Wekerle: The gut microbiota normally consists of specific bacteria, fungi and archaea. It is extremely important for the development of an intact immune system and maintenance of immune function. There is virtually a permanent dialog between the immune system and gut microbiota. This dialog is essential for the origin, development and function of the immune system.

How does a malfunctioning gut microbiota trigger an inflammation in a remote part of the body, as is the case with rheumatoid arthritis, type 1 diabetes or MS for example?

Wekerle: In a normal intestinal tract the dialog between bacteria and immune system causes a balance between the activation of inflammatory processes and a repression of this activation. In the case of dysbiosis, that being a change of the normal gut microbiota, this equilibrium becomes imbalanced. Suddenly, the inflammatory reaction types predominate. This can subsequently trigger inflammation in the intestinal tract or in other types of tissue outside of the intestinal tract.
Photo: white laboratory mouse is feeding

The microbiome, and with it indirectly also our diet, could play a role in the development of MS. Prof Wekerle and his colleague researched this with lab mice; © belchonok

How did you research this in the context of MS?

Wekerle: Several years ago, my colleagues and I developed a transgenic mouse model that spontaneously produced brain inflammation. It resembled MS in many aspects. We were interested in researching bacterial influences on the development of this spontaneous inflammation. This is why we transferred these mice into completely sterile environments, meaning they had no contact with bacteria on the skin and mucous membranes and they had no gut microbiota in particular. These mice did not develop spontaneous brain inflammation.

We followed this up with various tests by transferring cells and bacteria of mice kept in non-sterile environments to mice kept in sterile environments. The mice that were kept in sterile environments subsequently also developed brain inflammation. These tests suggest that under certain conditions, a healthy gut microbiota can trigger this type of autoimmune brain disease.

By comparison: what do we actually know today about the development of MS?

Wekerle: It requires a certain genetically encoded susceptibility to come down with MS. Exogenous stimuli also have to be added to this, that being environmental influences. We can infer this from epidemiological observations of sets of twins. In 20 to 30 percent of cases of identical twins, both twins come down with MS; in 70 to 80 percent it is only one of them. With fraternal twins who are actually genetically different, both twins contract the disease in only about five percent of cases.

On the one hand, this suggests that genetic factors indeed play a role. But since only one of the identical twins contracts the disease in 70 to 80 percent of cases, non-genetic, that is to say, environmental factors must also play a role.

What role would diet subsequently play in the development of MS?

Wekerle: Diet could play a very fundamental role by directly and indirectly influencing the immune system. First, specific components of our normal diet have a modulating effect on the immune system. Second, it can very fundamentally influence the composition of gut microbiota and change the structure of the different bacterial species. Third, our gut microbiota metabolizes a major portion of our nutrients. For their part, the resulting metabolites have an effect on the immune system. These relationships are currently being extensively researched.
Photo: Timo Roth; Copyright: B. Frommann

© B. Frommann

The interview was conducted by Timo Roth and translated from German by Elena O'Meara.