Gut-brain axis: Research links prebiotic diet to higher GABA levels

New research sheds light on the intricate connection between the gut microbiome and the brain, suggesting that a prebiotic diet might boost brain GABA (gamma-aminobutyric acid) levels, a key neurotransmitter associated with calming effects and neurological health.

GABA 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.

“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,” details study corresponding author Thunatchaporn Kumrungsee, associate professor at Hiroshima University’s Graduate School of Integrated Sciences for Life.

Dietary interventions on GABA

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.

The study authors aimed to assess how information directly passes between these two systems, asking: “Can an increase in gut-derived GABA directly cause an increase in the levels of brain GABA?”

The 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 — through which research has not yet proven GABA can pass.

Through trials on mice, researchers confirmed a “direct association” between gut GABA, brain GABA, and the gut microbiota.

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, the research team claims further studies indicate a potential for other pathways to cause an increase in brain GABA elevation, such as stimulation through the vagus nerve or hormonal pathways.

Prebiotics that elevate GABA

In trials conducted on mice, researchers identified fructo-oligosaccharides (FOS), non-digestible oligosaccharides, and Aspergillus-derived enzymes, lipase and protease, as prebiotics effective in elevating brain GABA through their influence on the gut. FOS significantly increased brain GABA in the mice’s cortex and hippocampus — regions where GABA acts to reduce excitability and induce calmness.

Additionally, FOS and enzyme supplementation also raised homocarnosine levels in the hippocampus.

“Food factors such as prebiotics and fungi-derived enzymes with prebiotic-like 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,” adds Kumrungsee.

Homocarnosine has also been linked to certain brain diseases, with a previous study by Kumrungsee showing that homocarnosine-deficient mice were more prone to exhibiting depression-like behaviors and instances of hyperactivity.

Despite the lack of confirmed data on a direct increase in brain GABA derived from gut microbiota, the study provides strong indications that prebiotic consumption may indeed increase the brain’s GABA levels.

Future research will focus on unraveling the precise mechanisms by which the gut influences the brain and identifying the specific pathways involved. Once clarified, the next objective will be to determine if the prebiotic treatments used in this study can be further employed to treat GABA-related diseases, such as epilepsy or depression.

The study is published in npj Science of Food.

Gut-brain axis research highlights

As interest in the human gut-brain axis picks up, the US FDA formally acknowledged the safety of Lactobacillus plantarum DR7 — a patented probiotic strain developed by Kaneka Probiotics and AB-Biotics. One study found DR7 modulated enzymes linked to neurotransmitter production, suggesting a role in supporting healthy serotonin and dopamine levels, two key chemicals that influence mood, cognition, and emotional well-being.

In May, a clinical study suggested that a combined intervention of a synbiotic and “gut-directed” hypnotherapy significantly reduces gastrointestinal discomfort, irritability, and anxiety symptoms in autistic children.

Meanwhile, in botanical innovations, a recent clinical paper in Nutrients demonstrated that ZenGut, a natural microalgae extract developed by Microphyt, relieves digestive discomfort while enhancing mood and mental well-being in healthy adults.