Gut Bacteria and GABA

Julia Malkowski, ND, DC | August 17, 2021

A beautiful concert exists between gut bacteria and neurotransmitters. As stress has increased during the current pandemic, Gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter (NT) has gained in popularity. Supplemental GABA and Gabapentin are well known as an anti-anxiolytic, stress remedy and sleep aid. Specific gut bacteria play a significant role in supporting the body’s supply of GABA. Emerging evidence suggests that addressing GABA from a gut perspective, concurrently with specific NT approaches, may prove to be most efficacious clinically.

In effort to better understand the symphony of interactions amongst gut bacteria and human physiology, germ-free models provide clues. Germ-free animals have been noted as having decreased serum GABA levels. At present we know that select gut bacteria directly produce colonic GABA, and others increase brain GABA. A variety of Lactobacillus spp., Bifidobacterium, as well as Streptococcus salivarius and thermophilus spp. have been noted to possess the ability to produce GABA. While Bacteriodes fragilis does not produce GABA, its presence is associated with increased GABA in the brain. Lactobacillus brevis has been shown to reduce anxiety and despair-like behaviors. Lactobacillus rhamnosus JB-1 has been noted to reduce depressive-and anxiety-like behaviors, and is gaining popularity as a psychobiotic bacteria that may confer a health benefit via the gut microbiota. 

This mechanism of action may lie in the Gut-Brain connection via a vagus-dependent manner, with specific changes in cerebral GABAergic activity. Furthermore, the influence of gut bacteria over anxiety is not seen in vagotomized models, thus strengthening this hypothesis. In a murine model, Lactobacillus rhamnosus JB-1 has been noted to increase GABA in cortical regions (cingulate and prelimbic) and reduce expression in the hippocampus, amygdala, and locus coeruleus. The same study noted that GABA receptors in the amygdala and hippocampus (GABAAα2 mRNA and GABAB1b mRNA) which are implicated in anxiety behaviors, were decreased in the presence of Lactobacillus rhamnosus JB-1. These patterns allow for behavioral responses consistent with anti-anxiolytic and antidepressant-like effects of GABA.

Experiences of stress have increased with current events. Many people are looking to decrease stress and anxiety as well as improve sleep, and may turn to GABA. Lactobacillus spp., Bifidobacterium, Streptococcus salivarius and thermophilus spp. have been noted to produce GABA, while the presence of Bacteriodes fragilis is associated with an increase in brain GABA. As bacteria have been noted to have psychobiotic effects, it is hypothesized the vagus nerve facilitates the gut-brain connection. After the gut bacteria increase GABA, this NT in turn increases bacterial abundance and diversity. Gut bacterial abundance and diversity is a key initial point in a multitude of physiological processes leading to homeostatic health outcomes. Although more research in this area is needed, emerging findings have promising implications. Benefits from addressing GABA may not stop at neurotransmitter outcomes. As GABA increases, it may even improve gut microbiome abundance and diversity to confer overall health benefits. 

 

References

Bravo, Javier A et al. “Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve.” Proceedings of the National Academy of Sciences of the United States of America vol. 108,38 (2011): 16050-5. doi:10.1073/pnas.1102999108

Hepsomali, P., Grieger, J., Nishihira J., et al. Effects of Oral Gamma-Aminobutyric Acid (GABA) Administration on Stress and Sleep in Humans: A Systematic Review. Front. Neurosci., (2020) https://doi.org/10.3389/fnins.2020.00923

Patterson, E., Ryan, P.M., Wiley, N. et al. Gamma-aminobutyric acid-producing lactobacilli positively affect metabolism and depressive-like behaviour in a mouse model of metabolic syndrome. Sci Rep 9, 16323 (2019). https://doi.org/10.1038/s41598-019-51781-x

Rafal J., Lynsie T., Stanisz, A., et al. Magnetic resonance spectroscopy reveals oral Lactobacillus promotion of increases in brain GABA, N-acetyl aspartate and glutamate. NeuroImage, (2016) https://doi.org/10.1016/j.neuroimage.2015.11.018

Strabdwitz, P., Neurotransmitter modulation by the gut microbiota. Brain Research, 1693 (2018) https://doi.org/10.1016/j.brainres.2018.03.015

Practical and Applicable Neuroendocrine Training for your Clinical Practice

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The Laboratory, Endocrine and Neurotransmitter Symposium (LENS) combines curriculum driven by research and real-world clinical scenarios, taught by engaging and seasoned practitioners and educators. Attendees return year after year to LENS to dive deep into neuroendocrine topics, leaving the weekend with a full toolkit of clinical tips, protocols, and practical applications that can be implemented right away in their practice. 

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Beyond the Basics: Comprehensive Neurotransmitter Primer

Ruth Hobson, ND

September 1, 2021 at 9:30 AM and 12 PM Pacific

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