‘Surprising’ impact of gut bacteria on gene expression in the brain

Gut-brain axis: Gene regulation may be link between gut bacteria and anxiety

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The trillions of microbes in our gut can have a dramatic influence on microRNAs that regulate gene expression in parts of the brain including those related to fear and anxiety, new data suggests.

The findings come from research performed at Cork’s APC Microbiome Institute, which investigated the link between gut bacteria and biological molecules called microRNAs (miRNAs) in the brain.

Led by Dr Gerard Clarke and Professor John F. Cryan, the team reported that the trillions of bacteria within the gastrointestinal tract can influence microRNAs (miRNAs) in areas of the brain linked to fear, anxiety, social function and depression.

According to the data, published in the journal Microbiome, mice and rats that had either no gut microbes at all or depleted gut microbes were found to have an altered miRNA expression profile in the amygdala and prefrontal cortex brain regions.

The amygdala is responsible for the emotional response to fear stimuli, while the prefrontal cortex is key to higher cognitive functions and in the expression of anxiety and social behaviours.

Furthermore, the APC researchers were able to show that some of the dysregulation of miRNA seen could be reversed by adding back the gut microbiome later in life. However, they added that a number of miRNAs remained altered following exposure to microbes - which supports the concept of critical neurodevelopmental windows during which the gut microbiota is essential in influencing brain development.

 "Gut microbes seem to influence miRNAs in the amygdala and the prefrontal cortex. This is important because these miRNAs may affect physiological processes that are fundamental to the functioning of the central nervous system and in brain regions, such as the amygdala and prefrontal cortex, which are heavily implicated in anxiety and depression,” said Clarke.

He added that altered expression miRNAs, as seen in this study, has also previously been linked to neuronal survival, growth and development, as well as neurogenesis – which are all important targets for the treatment of stress-related psychiatric disorders. 

miRNA modulation

The team reported changes to levels of 103 miRNAs in the amygdala and 31 in the prefrontal cortex of mice reared without gut bacteria (GF mice) compared to conventional mice.

Adding back the gut microbiome later in life normalised some of the changes to miRNAs in the brain.

Clarke and colleagues also found that depleting the microbiota of adult rats with antibiotics impacted some miRNAs in the brain in a similar way to the germ-free mice.

This suggests that even if a healthy microbiota is present in early life, subsequent changes in adulthood can impact miRNAs in the brain relevant to anxiety-like behaviours, according to the authors.

“The Psychobiotic Revolution is coming … and we can now add miRNAs to an expanding range of therapeutic targets in the brain that can potentially be controlled by manipulating the bacteria in our gastrointestinal tract,” commented Professor Cryan.

However, both Clarke and Cryan cautioned that more work is needed before the full benefits and implications of the work can be moved into a clinical setting, and that a more advanced understanding of the underlying mechanisms are needed before progress can be made. 

"This is early stage research but the possibility of achieving the desired impact on miRNAs in specific brain regions by targeting the gut microbiota -- for example by using psychobiotics -- is an appealing prospect,” said Clarke.

Source: Microbiome
Published online, Open Access, doi: 10.1186/s40168-017-0321-3
“Microbial regulation of microRNA expression in the amygdala and prefrontal cortex”
Authors: Alan E. Hoban, et al

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