Study finds evidence that gut microbiome regulates brain response to fear

The community of microorganisms living in your gut may influence anxiety disorders. New research suggests that the gut microbiome plays an important role in fear responses.

“Over the last decade or so, we and others have provided a substantial catalogue of evidence to support the concept that the gut microbiome can tune brain function and behaviour,” explained the study’s corresponding author, Gerard Clarke of the University College Cork. “It is quite remarkable to see the broad scope of this influence and we are very excited to be involved in this new area of research. This study was prompted by the desire to try and pinpoint the brain regions that might be involved in microbial regulation of fear and fear-associated memories.

“Our interest in this topic is also spurred by the desire to develop new therapeutic targets to tackle fear-related disorders.”

Previous research had established two important points: that the brain structure known as the amygdala plays a key role in anxiety disorders and that gut microbiota can influence behavior.

By using microbiota-depleted mice in a classic fear conditioning model, the researchers were able to determine that fear memory relies on the presence of a functional microbiota in rodents. The microbiota-depleted mice had trouble learning to associate a tone with an electric shock. But exposure to environmental microbes appeared to reverse their deficit in memory retention.

“We need to gain a better understanding of the factors that regulate fear and fear-associated memories,” Clarke told PsyPost. “The memory of a traumatic event, for example, is hard to shake and this study suggests that our gut microbes play a role in this fear memory recall. If this translates from mouse to man, it could pave the way for therapeutic targeting of the gut microbiome to control the excessive expression of fear and anxiety.

“Fear itself is a normal response that can sometimes go awry and in the brain, the amygdala is a very important region in this response. This study also shows that our gut microbes can dial into the amygdala to exert an influence over the function of this brain region.”

The researchers also found evidence of neuronal hyperactivity in the amygdala of microbiota-depleted mice.

“It’s important to note that this research is at an early stage and that it was carried out in germ-free animals,” Clarke said. “These animals lack a gut microbiota for their entire lives and although a great way to assess the consequences for brain and behaviour of growing up germ free, there is no direct clinical equivalent – after all, very few people grow up in a sterile bubble! However, the fact that the altered fear-memory recall can be at least partially restored when gut microbes are introduced post-weaning in these animals is an important aspect of the study and we now plan to assess this gut-brain signalling pathway following less extreme gut microbiota manipulations.”

“The next steps in this research also involve assessing how the gut signals to the brain in general and to the amygdala specifically to regulate the fear response. Gathering this information will help identify strategies to target the microbiome to generate novel efficacious treatments for fear-related disorders.”

“One of the main reasons our ambitions for this study came to fruition is down to the dedication and skill of the PhD student who worked on the study, Dr Alan Hoban (first author),” Clarke added. “I would like to acknowledge the support of Science Foundation Ireland and the Brain and Behaviour Research Foundation towards the completion of this study.”

The study, “The microbiome regulates amygdala-dependent fear recall“, was published May 16, 2017, in the journal Molecular Psychiatry.