Gut instincts

10 May 2011

Understanding the intimate connections between microbes and development could lead to better treatment of disease

Autoradiograms showing the supressed expression of anxiety and synaptic plasticity-related genes in the brains of germ-free mice (right) compared with wild-type mice (left).

Autoradiograms showing the supressed expression of anxiety and synaptic plasticity-related genes in the brains of germ-free mice (right) compared with wild-type mice (left).

© 2011 R. D. Heijtz, S. Petersson

Microbes in the gut can influence their mammal hosts in far-reaching ways, even affecting brain development in newborn mammals and subsequent adult behavior. Martin Hibberd, Sven Pettersson and co-workers at the A*STAR Genome Institute of Singapore and Karolinska Institutet in Switzerland have now shown that gut microorganisms impact motor activity and anxiety behavior by affecting the development of nerve connections. Their findings have implications for the causes and treatment of a range of conditions, including mental illness.

Any environmental influence on early development can have a profound effect on the resulting adult organism. Previous studies have shown that the wide diversity of microorganisms adapted to live in the mammal gut has an impact not only on the digestive system, but also on the function of the liver, as well as the development of nearby blood vessels and of the immune system. With respect to the brain, microbes are suspected to have an association with common developmental disorders that lead to autism and schizophrenia.

Hibberd, Pettersson and their co-workers decided to check if the normal microbes of the gut exert any impact on the development of the brain. They did so by comparing the exploratory activity and anxiety behavior of germ-free (GF) mice—mice raised in an ultraclean environment devoid of germs—with the behavior of normal healthy mice, known as specific pathogen free (SPF) mice, carrying a typical load of gut microbes. They also tested a third group—GF mice exposed to gut microbes early in life.

The researchers found that when placed in a novel environment, in this case an open-field activity box, GF mice moved around, reared and explored the central area significantly more than SPF mice. And in a box with light and dark areas, the GF mice spent significantly more time in the light. The GF mice with gut microbes behaved in a similar way to SPF mice.

The researchers then studied gene activity and levels of compounds specifically associated with the formation of nerve connections or synapses in the part of the forebrain known as the striatum. There were significant differences between the mice with gut microorganisms and those without (see image). Overall the researchers concluded that the colonization of the gut by microbes affects the development of the nerve circuits involved in the control of motor activity and anxiety behavior.

“Understanding the close environmental interaction between bacteria and mammals may illuminate its role in several diseases,” says Hibberd. “And those conditions may become amenable to treatment by altering gut bacteria.”

The A*STAR-affiliated researchers contributing to this research are from the Genome Institute of Singapore.

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Heijtz, R. D. et al. Normal gut microbiota modulates brain development and behavior. Proceedings of the National Academy of Sciences 108, 3047–3052 (2011). | article

This article was made for A*STAR Research by Nature Research Custom Media, part of Springer Nature