Gut Microbiota Regulate Social Behaviour

Post by Lina Teichmann

What's the science?

Communication between the gut and the brain can affect social interactions between mice. For example, mice selectively bred without gut microbiomes (germ-free mice) display reduced social behavior towards stranger mice. Similarly, in humans there is evidence for a link between gut bacteria and psychiatric disorders that affect social behavior. This week in Nature, Wu examined how gut microbiota modulate social behavior in mice and showed that specific gut bacteria influence social behavior by modulating stress responses in the brain.

How did they do it?

A group of germ-free mice without gut microbiomes and a group of mice that were treated with antibiotics to deplete gut microbiomes were compared to specific-pathogen-free control mice. The social activity of the different mice was observed and assessed. In addition, neuronal activation in several brain regions was tested after the mice had social encounters, and corticosterone (stress hormone) levels were measured. The researchers also examined whether artificially reducing corticosterone production can change the degree of social activity in germ-free and antibiotic-treated mice. To identify which species of bacteria are involved in reducing stress after social interactions, microbiome profiling and in vivo selection were used.

What did they find?

Germ-free and antibiotic-treated mice displayed reduced social behavior towards new mice. In addition, several brain regions involved in stress responses such as the paraventricular nucleus of the hypothalamus, the bed nucleus of stria terminalis, and the hippocampal dentate gyrus showed increased activity after social interaction. Increased levels of corticosterone were found in germ-free and antibiotic-treated mice after social encounters with stranger mice, indicating higher stress levels. If corticosterone was reduced by surgically removing the adrenal gland or using pharmacological inhibitors, sociability could be restored in the microbiome-depleted mice. Similarly, removing glucocorticoid receptors, using glucocorticoid receptor antagonists, or inactivating specific neurons in the paraventricular nucleus of the hypothalamus restored social impairments in the antibiotic-treated mice. Lastly, the authors found that a specific bacterial species, Enterococcus faecalis, was involved in reducing corticosterone levels after social interactions.

What's the impact?

The findings demonstrate that specific gut bacteria in mice lead to reduced production of corticosterone to suppress stress responses when new mice are encountered. The current work identifies a neural circuit that responds to gut bacteria and demonstrates how sociability can be restored in gut microbiota depleted mice. These findings provide new insight into the gut-brain connection, and may help in the development of treatments for disorders affecting social behavior.

Wu et al. Microbiota regulate social behaviour via stress response neurons in the brain, Nature (2021). Access the original scientific publication here.