Research published in the open access journal Microbiome sheds new light on how gut bacteria may influence anxiety-like behaviors. 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. These mice are reared in a germ-free bubble and typically display abnormal anxiety, deficits in sociability and cognition, and increased depressive-like behaviors.

Dr Gerard Clarke, the corresponding author said: "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."

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

Dr Clarke said: "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. 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. 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 10-12 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.

Dr Clarke said: "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."

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Notes to editors:

1. Research article:

Microbial regulation of microRNA expression in the amygdala and prefrontal cortex

Hoban et al. Microbiome 2017

DOI: 10.1186/s40168-017-0321-3

For an embargoed copy of the research article please contact Anne Korn at BioMed Central.

After the embargo lifts, the article will be available at the journal website: https:/ / microbiomejournal. biomedcentral. com/ articles/ 10. 1186/ s40168-017-0321-3

Please name the journal in any story you write. If you are writing for the web, please link to the article. All articles are available free of charge, according to BioMed Central's open access policy.

2. The central purpose of Microbiome is to unite investigators conducting microbiome research in environmental, agricultural, and biomedical arenas.

Topics broadly addressing the study of microbial communities, such as, microbial surveys, bioinformatics, meta-omics approaches and community/host interaction modeling will be considered for publication. Through this collection of literature Microbiome hopes to integrate researchers with common scientific objectives across a broad cross-section of sub-disciplines within microbial ecology.

3. A pioneer of open access publishing, BMC has an evolving portfolio of high quality peer-reviewed journals including broad interest titles such as BMC Biology and BMC Medicine, specialist journals such as Malaria Journal and Microbiome, and the BMC series.

At BMC, research is always in progress. We are committed to continual innovation to better support the needs of our communities, ensuring the integrity of the research we publish, and championing the benefits of open research. BMC is part of Springer Nature, giving us greater opportunities to help authors connect and advance discoveries across the world.

4. About APC Microbiome Institute:

The APC Microbiome Institute (APC) was formed in 2003 with funding from Science Foundation Ireland and in conjunction with key industry partners. It represents a seamless collaboration between University College Cork, Teagasc (the Irish Agriculture and Food Development Authority) and Cork Institute of Technology. It is widely recognised that the gut microbiota plays an important role in human health and has become one of the most dynamic, complex and exciting areas of research in both food and pharmaceutical arenas. Over the last decade the APC has established itself as one of the leading global centres in gut microbiota research. The APC has made several landmark discoveries and has published over 1,000 research articles in peer-reviewed journals, generating many journal covers and associated editorials. The APC comprises over 300 individuals, from the scientific PI's (the APC Faculty) funded by the partner Institutions, the management team, and a dedicated group of research scientists, research assistants and postgraduates students.

5. About Brain & Behaviour Research Foundation:

The Brain & Behavior Research Foundation (BBRF) began as a family movement in 1981 and has since become the world's leading private funder of mental health research. Since awarding the first NARSAD Grant in 1987, the Brain & Behavior Research Foundation has awarded more than $365 million to fund more than 5,000 grants to more than 4,000 scientists around the world. The BBRF is committed to alleviating the suffering caused by mental illness by awarding grants that will lead to advances and breakthroughs in scientific research.