Rodent Study: How Gut Bacteria May Impact Anxiety

A new study from Ireland on rodents shows that certain brain regions heavily implicated in anxiety and depression are significantly affected by gut microbes by way of biological molecules called microRNAs (miRNAs).

The findings, published in the journal Microbiome, shed new light on how gut bacteria may influence anxiety-like behaviors.

The researchers from APC Microbiome Institute at University College Cork studied the link between gut bacteria and miRNAs in the brain and discovered that a significant number of miRNAs were changed in the brains of microbe-free mice. These mice, who had been raised in a germ-free bubble, displayed abnormal anxiety, deficits in sociability and cognition and increased depressive-like behaviors.

“Gut microbes seem to influence miRNAs in the amygdala and the prefrontal cortex,” said Dr. Gerard Clarke, the corresponding author.

“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.”

miRNAs are short sequences of nucleotides (the building blocks of DNA and RNA), which can influence how genes are expressed. Dysregulation or dysfunction of these molecules is believed to be an underlying factor contributing to stress-related mental disorders, neurodegenerative diseases and neurodevelopmental abnormalities. In addition, miRNA changes in the brain have been implicated in anxiety-like behaviors.

“It may be possible to modulate miRNAs in the brain for the treatment of psychiatric disorders but research in this area has faced several challenges, for example, finding safe and biologically stable compounds that are able to cross the blood-brain barrier and then act at the desired location in the brain,” said Clarke.

“Our study suggests that some of the hurdles that stand in the way of exploiting the therapeutic potential of miRNAs could be cleared by instead targeting the gut microbiome.”

The findings reveal that levels of 103 miRNAs were different in the amygdala and 31 in the prefrontal cortex of mice raised without gut bacteria (GF mice) compared to conventional mice. However, adding back the gut microbiome later in life normalized some of the changes to miRNAs in the brain.

The study suggests that a healthy microbiome is necessary for appropriate regulation of miRNAs in these brain regions. Prior research has shown that manipulation of the gut microbiome influences anxiety-like behaviors but this is the first time that the gut microbiome has been linked to miRNAs in both the amygdala and prefrontal cortex, according to the authors.

To determine which miRNAs were present in the amygdala and the prefrontal cortex, the researchers used next-generation-sequencing (NGS) on groups of 10-12 control mice with a normal gut microbiota, GF mice and ex-GF mice — colonized with bacteria by housing them with the control mice — and adult rats whose normal microbiota had been depleted with antibiotics.

The researchers discovered that depleting the microbiota of adult rats with antibiotics affected some miRNAs in the brain in a similar way to the GF 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 behaviors, according to the authors.

The exact mechanism by which the gut microbiota is able to influence the miRNAs in the brain is still unclear, say the researchers. And while the study shows that effects of the microbiota on miRNAs are present in more than one species (mice and rats), further research into the association between gut bacteria, miRNAs and anxiety-like behaviors is needed before the findings can be translated to a clinical setting.

“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: BioMed Central