Lactococcus lactis NCDO2118 produces anti-hypertensive GABA and exerts acute hypotensive in spontaneously hypertensive rats

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Tessália Diniz Luerce Saraiva Gisele Maia Etelvino Mariana Oliveira Cassiana Severiano de Sousa Marcela Santiago Pacheco de Azevedo Alejandra de Moreno de LeBlanc Jean Guy LeBlanc Debmalya Barh Preetam Ghosh Franco Venanzi Henrique Cesar Pereira Figueiredo Robson Augusto Souza Santos Vasco Ariston de Carvalho Azevedo


Gamma (γ)-aminobutyric acid (GABA) is a molecule with nutraceutical interest since it is recognized for its health-promoting properties such as hypotensive effects. Some lactic acid bacteria (LAB) have been shown to be able to produce GABA. In the present investigation, Lactococcus (L.) lactis NCDO2118, a probiotic LAB, was cultured in a medium supplemented with different concentration of glutamate, the substrate for GABA production. This strain was evaluated in SHRSP (Spontaneously Hypertensive Stroke-Prone Rats) to assess its hypotensive effect. The evaluation showed that GABA production is variable depending on the glutamate concentration and incubation time and that the increased GABA production potentiates its hypotensive effect. This work demonstrates that L. lactis NCDO 2118 could be used as a tool for developing health-promoting foods, such as those enriched with GABA as an interesting and novel pharmacological strategy.

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SARAIVA, Tessália Diniz Luerce et al. Lactococcus lactis NCDO2118 produces anti-hypertensive GABA and exerts acute hypotensive in spontaneously hypertensive rats. Medical Research Archives, [S.l.], v. 4, n. 7, nov. 2016. ISSN 2375-1924. Available at: <>. Date accessed: 20 jan. 2018.
Lactococcus lactis; Gamma-AminoButyric Acid; GABA; Glutamic Acid Decarboxylase; GAD; Hypertension
Research Articles


Auteri, M., Zizzo, M. G., & Serio, R. (2015). GABA and GABA receptors in the gastrointestinal tract: from motility to inflammation. Pharmacological Research, 93, 11–21.

Becerra-Tomás, N., Guasch-Ferré, M., Quilez, J., Merino, J., Ferré, R., Díaz-López, A., … Salas-Salvadó, J. (2015). Effect of Functional Bread Rich in Potassium, γ-Aminobutyric Acid and Angiotensin-Converting Enzyme Inhibitors on Blood Pressure, Glucose Metabolism and Endothelial Function: A Double-blind Randomized Crossover Clinical Trial. Medicine, 94(46), e1807.

Boonstra, E., de Kleijn, R., Colzato, L. S., Alkemade, A., Forstmann, B. U., & Nieuwenhuis, S. (2015). Neurotransmitters as food supplements: the effects of GABA on brain and behavior. Frontiers in Psychology, 6.

Bravo, J. A., Forsythe, P., Chew, M. V., Escaravage, E., Savignac, H. M., Dinan, T. G., … Cryan, J. F. (2011). 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, 108(38), 16050–16055.

Chang, C.-T., Hsu, C.-K., Chou, S.-T., Chen, Y.-C., Huang, F.-S., & Chung, Y.-C. (2009). Effect of fermentation time on the antioxidant activities of tempeh prepared from fermented soybean using Rhizopus oligosporus. International Journal of Food Science & Technology, 44(4), 799–806.

Cryan, J., & Kaupmann, K. (2005). Don’t worry “B” happy!: a role for GABA(B) receptors in anxiety and depression. Trends in Pharmacological Sciences, 26(1), 36–43.

Dhakal, R., Bajpai, V. K., & Baek, K.-H. (2012). Production of gaba (&#947; - aminobutyric acid) by microorganisms: a review. Brazilian Journal of Microbiology, 43(4), 1230–1241.

Elliott, K., & Hobbiger, F. (1959). Gamma aminobutyric acid: circulatory and respiratory effects in different species: re-investigation of the anti-strychnine action in mice. The Journal of Physiology, 146, 74–80.

Fatemi, S. H., Folsom, T. D., Rooney, R. J., & Thuras, P. D. (2013). Expression of GABAA α2-, β1- and ɛ-receptors are altered significantly in the lateral cerebellum of subjects with schizophrenia, major depression and bipolar disorder. Translational Psychiatry, 3(9), e303.

Feehily, C., & Karatzas, K. A. G. (2013). Role of glutamate metabolism in bacterial responses towards acid and other stresses. Journal of Applied Microbiology, 114(1), 11–24.

Gomaa, E. Z. (2015). Enhancement of γ-Amminobutyric Acid Production by Co-Culturing of Two Lactobacilli Strains. Asian Journal of Biotechnology, 7(3), 108–118.

Hayakawa, K., Kimura, M., & Kamata, K. (2002). Mechanism underlying γ-aminobutyric acid-induced antihypertensive effect in spontaneously hypertensive rats. European Journal of Pharmacology, 438(1-2), 107–113.

Hayakawa, K., Kimura, M., Kasaha, K., Matsumoto, K., Sansawa, H., & Yamori, Y. (2004). Effect of a γ-aminobutyric acid-enriched dairy product on the blood pressure of spontaneously hypertensive and normotensive Wistar–Kyoto rats. British Journal of Nutrition, 92(03), 411.

Higuchi, T., Hayashi, H., & Abe, K. (1997). Exchange of glutamate and gamma-aminobutyrate in a Lactobacillus strain. Journal of Bacteriology, 179(10), 3362–3364.

Inoue, K., Shirai, T., Ochiai, H., Kasao, M., Hayakawa, K., Kimura, M., & Sansawa, H. (2003). Blood-pressure-lowering effect of a novel fermented milk containing γ-aminobutyric acid (GABA) in mild hypertensives. European Journal of Clinical Nutrition, 57(3), 490–495.

Kim, J. Y., Lee, M. Y., Ji, G. E., Lee, Y. S., & Hwang, K. T. (2009). Production of γ-aminobutyric acid in black raspberry juice during fermentation by Lactobacillus brevis GABA100. International Journal of Food Microbiology, 130(1), 12–16.

Kook, M.-C., & Cho, S.-C. (2013). Production of GABA (gamma amino butyric acid) by Lactic Acid Bacteria. Korean Journal for Food Science of Animal Resources, 33(3), 377–389.

Krasowski, M. D., & Harrison, N. L. (2000). The actions of ether, alcohol and alkane general anaesthetics on GABA A and glycine receptors and the effects of TM2 and TM3 mutations. British Journal of Pharmacology, 129(4), 731–743.

Krogsgaard-Larsen, P., Falch, E., Larsson, O., & Schousboe, A. (1987). GABA uptake inhibitors: relevance to antiepileptic drug research. Epilepsy Research, 1(2), 77–93.

Li, H., & Cao, Y. (2010). Lactic acid bacterial cell factories for gamma-aminobutyric acid. Amino Acids, 39(5), 1107–1116.

Li, H., Qiu, T., Huang, G., & Cao, Y. (2010). Production of gamma-aminobutyric acid by Lactobacillus brevis NCL912 using fed-batch fermentation. Microbial Cell Factories, 9(1), 85.

Masineni, S., Chander, P., Singh, G., Powers, C., & Stierjr, C. (2005). Male Gender and Not the Severity of Hypertension Is Associated With End-Organ Damage in Aged Stroke-Prone Spontaneously Hypertensive Rats. American Journal of Hypertension, 18(6), 878–884.

Mazzoli, R., Pessione, E., Dufour, M., Laroute, V., Giuffrida, M. G., Giunta, C., … Loubière, P. (2010). Glutamate-induced metabolic changes in Lactococcus lactis NCDO 2118 during GABA production: combined transcriptomic and proteomic analysis. Amino Acids, 39(3), 727–737.

Meyer, R., & Fish, R. (2005). A review of tribromoethanol anesthesia for production of genetically engineered mice and rats. Lab Animal, 34(10), 47–52.

Mody, I., De Koninck, Y., Otis, T. S., & Soltesz, I. (1994). Bridging the cleft at GABA synapses in the brain. Trends in Neurosciences, 17(12), 517–525.

Park, K.-B., & Oh, S.-H. (2007). Production of yogurt with enhanced levels of gamma-aminobutyric acid and valuable nutrients using lactic acid bacteria and germinated soybean extract. Bioresource Technology, 98(8), 1675–1679.

Poulter, M. O., Singhal, R., Brown, L. A., & Krantis, A. (1999). GABAA receptor subunit messenger RNA expression in the enteric nervous system of the rat: implications for functional diversity of enteric GABAA receptors. Neuroscience, 93(3), 1159–1165.

Roberts, E., & Frankel, S. (1950). γ-Aminobutyric acid in brain. Federation Proceedings, (9), 219.
Sanders, M. E. (1998). Overview of Functional Foods: Emphasis on Probiotic Bacteria. International Dairy Journal, 8(5-6), 341–347.

Sasaki, H., Muramoto, O., Kanazawa, I., Arai, H., Kosaka, K., & Iizuka, R. (1986). Regional distribution of amino acid transmitters in postmortem brains of presenile and senile dementia of Alzheimer type. Annals of Neurology, 19(3), 263–269.

Sauguet, L., Howard, R. J., Malherbe, L., Lee, U. S., Corringer, P.-J., Adron Harris, R., & Delarue, M. (2013). Structural basis for potentiation by alcohols and anaesthetics in a ligand-gated ion channel. Nature Communications, 4, 1697.

Schousboe, A., & Waagepetersen, H. S. (2007). GABA: Homeostatic and pharmacological aspects. In Progress in Brain Research (Vol. 160, pp. 9–19). Elsevier. Retrieved from

Seok, J., Park, K., Kim, Y., Bae, M., Lee, M., & Oh, S. (2008). Production and Characterization of Kimchi with Enhanced Levels of γ-Aminobutyric Acid, 17(5).

Stanton, H. (1963). Mode of action of gamma amino butyric acid on the cardiovascular system. Archives Internationales de Pharmacodynamie et de Thérapie, 143, 195–204.

Takahashi, H., Tiba, M., Iino, M., & Takayasu, T. (1955). The effect of g-aminobutyric acid on blood pressure. The Japanese Journal of Physiology, 5, 334–341.

Takayama, M., & Ezura, H. (2015). How and why does tomato accumulate a large amount of GABA in the fruit? Frontiers in Plant Science, 6.

Thwaites, D. T., Basterfield, L., McCleave, P. M. J., Carter, S. M., & Simmons, N. L. (2000). Gamma-aminobutyric acid (GABA) transport across human intestinal epithelial (Caco-2) cell monolayers. British Journal of Pharmacology, 129(3), 457–464.

Tsukatani, T., Higuchi, T., & Matsumoto, k. (2005). Enzyme-based microtiter plate assay for γ-aminobutyric acid: application to the screening of γ -aminobutyric acid-producing lactic acid bacteria. Analytica Chimica Acta, 540, 293–297.

Waagepetersen, H. S., Sonnewald, U., & Schousboe, A. (2002). The GABA Paradox: Multiple Roles as Metabolite, Neurotransmitter, and Neurodifferentiative Agent. Journal of Neurochemistry, 73(4), 1335–1342.
World Health Organization. (2013). A Global Brief on Hypertension: Silent Killer, Global Public Health Crisis (online). Retrieved from

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