25 Aug 2017 --- Research published in the open access journal Microbiome has further explained how gut bacteria may influence anxiety-like behaviors by investigating the link between gut bacteria and biological molecules called microRNAs (miRNAs) in the brain.
Researchers at the APC Microbiome Institute at University College Cork – which is funded by Science Foundation Ireland – found that a significant number of miRNAs were changed in the brains of microbe-free mice. The mice are reared in a germ-free bubble and typically display abnormal anxiety, deficits in sociability and cognition, and increased depressive-like behaviors.
“Such findings bring yet [more] evidence of the tight link between the microbiota and the brain and indicate new pathway of communication between the two,” Sylvie Roquefeuil, Communications and PR Manager at Lallemand Animal Nutrition, tells NutritionInsight. “This is an area we have been exploring for a decade now with animal and clinical research showing the effects of specific probiotics strains and formulas on stress and anxiety.
“In 2010 a randomized double-blind placebo-controlled study (Messaoudi et al.) demonstrated that Probio’Stick formula could help moderate general feelings of anxiety and promote a healthy mood balance in healthy subjects experiencing mild to moderate stress resulting from life events,” continues Roquefeuil. “In rats, this formula showed anxiolytic-like effect in stress condition since the effect was comparable to Diazepam, without the potential side-effects of this type of drugs.”
Importance of miRNAs “Gut microbes seem to influence miRNAs in the amygdala and the prefrontal cortex,” observes Dr. Gerard Clarke, the corresponding author of the APC Microbiome Institute study. “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.”
“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,” Dr. Clarke adds.
The miRNAs mentioned are short sequences of nucleotides (the building blocks of DNA and RNA), which can act to control how genes are expressed. Nowadays, miRNA dysregulation or dysfunction is believed to be an underlying factor contributing to stress-related psychiatric disorders, neurodegenerative diseases and neurodevelopmental abnormalities, according to the BioMed Central press release. Indeed, 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,” Dr. Clarke says. “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 researchers found that levels of 103 miRNAs were different 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 normalized some of the changes to miRNAs in the brain.
The findings suggest that a healthy microbiome is necessary for appropriate regulation of miRNAs in these brain regions, the BioMed Central press release notes. Previous research demonstrated that manipulation of the gut microbiome affects 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.
The researchers used next-generation-sequencing (NGS) to find out which miRNAs were present in the amygdala and the prefrontal cortex of groups of 10 to 12 control mice with a normal gut microbiota, GF mice and ex-GF mice – which had been colonized with bacteria by housing them with the control mice – and adult rats whose normal microbiota had been depleted with antibiotics.
They found that depleting the microbiota of adult rats with antibiotics impacted 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 authors note that the exact mechanism by which the gut microbiota is able to influence the miRNAs in the brain remains unclear. Even though the study shows that effects of the microbiota on miRNAs are present in more than one species (mice and rats), further research into the possible connection between gut bacteria, miRNAs and anxiety-like behaviors is needed before the findings can be translated to a clinical setting.
Neverthleless, Roquefeuil says of the study’s future implications: “This offers interesting potential for the future, I think we are only at the beginning of a very interesting journey in this area.”
The research article from Microbiome can be found here.
By Paul Creasy
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