Prebiotics might be a factor in preventing or treating issues caused by low brain GABA

(Press-News.org) GABA, or gamma-aminobutyric acid, is an amino acid functioning as the principal inhibitory neurotransmitter that can act on the brain to slow or stop the reception of certain signals to the brain, leading to a calmer and more relaxed state. Low GABA levels in the brain have been associated with neurological disorders and diseases like depression, Alzheimer's or epilepsy. Recently, there has been a push towards understanding more about the gut’s influence on mood, behavior and mental health, as well as what foods might fuel or hinder a healthy mind. Researchers set to work on determining whether brain GABA levels can be increased through dietary additions with the aim of modulating the gut bacteria present in an individual to bypass the blood-brain barrier, a barrier in which it is not proven yet GABA can pass through.

Results were published in npj Science of Food in April 2025.

The relationship between the gut and brain is not necessarily a newly established one, but one that is gaining more attention and influence in how science looks at treating the body more holistically. The two systems communicate effectively, but researchers wanted to know the answer of just how directly these two systems can pass information: can an increase in gut-derived GABA directly cause an increase in the levels of brain GABA?  

Researchers confirmed a direct association between gut GABA, brain GABA and the gut microbiota through trials on mice. There are still no solid results on whether or not gut microbiota-derived GABA can cross the blood-brain barrier and directly increase brain GABA. However, further studies do indicate a potential for other pathways to cause an increase in brain GABA elevation, such as stimulation through the Vagus nerve or hormonal pathways.

“Our study suggests that prebiotics have the ability to prevent or treat those brain diseases by increasing brain GABA levels via promoting gut GABA production through modulating gut microbiota,” said study corresponding author Thunatchaporn Kumrungsee, associate professor at Hiroshima University’s Graduate School of Integrated Sciences for Life.

In trials done on mice, researchers found the fructo-oligosaccarides (FOS), non-digestible oligosaccharides, and Aspergillus-derived enzymes, lipase and protease, as prebiotics that have shown effective in elevation brain GABA through the influence on the gut. FOS appeared to have a significant increase on the mice’s brain GABA in both the cortex and hippocampus, both sites where GABA acts to reduce excitability and induce a sense of calmness. Additionally, FOS and enzyme supplementation also raised homocarnosine levels in the hippocampus.

“Food factors such as prebiotics and fungi-derived enzymes with prebiotic-liked effects have an ability to increase brain GABA and homocarnosine, a GABA-containing brain-specific peptide, which can possibly in turn enhance brain health through gut microbiota modulation,” said Kumrungsee.

Homocarnosine appears to also be linked to some of the same brain diseases, with a previous study by Kumrungsee indicating homocarnosine-deficient mice were more prone to exhibiting depression-like behaviors and instances of hyperactivity.

Despite a lack of confirmed data on an increase in GABA in the brain derived directly from gut microbiota, there is good reason to believe prebiotic consumption might increase the brain’s GABA levels, as shown in the study. Researchers still need to unravel the mechanism by which the gut might influence the brain and what pathway might be responsible. Once clarified, the next goal is to figure out if the prebiotic treatment used in the study can be further employed for the treatment of GABA-related diseases, like epilepsy or depression.  

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Jason D. Braga, Norihisa Kato, Noriyuki Yanaka and Thanutchaporn Kumrungsee of the Program of Food and AgriLife Science at Hiroshima University with Jason D. Braga also of the Institute of Food Science and Technology at Cavite State University, Yongshou Yang of the School of Life Sciences at Anhui University, Kyoichi Nishio, Masasumi Okada, Manabu Kuroda and Shotaro Yamaguchi of Amano Enzyme Inc. and Thunatchaporn Kumrungsee of Smart Agriculture at Hiroshima University contributed to this research.

This research was made possible by the Japanese Society of Functional Fermented Foods and Enzyme Supplements, the Danone Institute of Japan Foundation research grant, the Japanese Ministry of Education, Culture, Sports, Science and Technology, and Amano Enzyme Inc.

This paper received funding from Hiroshima University to cover open access fees.

About Hiroshima University

Since its foundation in 1949, Hiroshima University has striven to become one of the most prominent and comprehensive universities in Japan for the promotion and development of scholarship and education. Consisting of 12 schools for undergraduate level and 5 graduate schools, ranging from natural sciences to humanities and social sciences, the university has grown into one of the most distinguished comprehensive research universities in Japan. English website: https://www.hiroshima-u.ac.jp/en

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