Biological diversity of animal-associated lactic acid bacteria as natural producers of gamma-aminobutyric acid (GABA)
DOI:
https://doi.org/10.5281/zenodo.18208165Keywords:
Animal-associated microbiota, lactic acid bacteria, biodiversity, gamma-aminobutyric acid (GABA), glutamate decarboxylaseAbstract
Gamma-aminobutyric acid (GABA) is a crucial bioactive compound widely distributed in animal nervous systems, where it serves as the primary inhibitory neurotransmitter and plays a pivotal role in regulating physiological and behavioral processes. In recent years, increasing attention has been directed toward natural, biodiversity-based sources of GABA, particularly microorganisms associated with animals and animal-derived environments. Lactic acid bacteria (LAB), commonly occurring in animal gastrointestinal microbiota and traditional animal-based fermented foods, represent an important but underexplored component of animal-associated microbial biodiversity. This review synthesizes current knowledge on the diversity of animal-associated LAB capable of GABA biosynthesis and highlights their ecological, genetic, and functional significance. Special emphasis is placed on the glutamate decarboxylase (GAD) system (gadA, gadB, and gadC genes), which enables LAB to convert L-glutamate into GABA as part of an acid-resistance mechanism essential for survival in animal-related niches. Comparative analysis of published studies reveals substantial interspecific and intraspecific variation in GABA production among LAB species, with Lactobacillus brevis, L. paracasei, and L. buchneri emerging as prominent GABA producers. Optimal GABA synthesis is generally associated with acidic conditions, moderate temperatures, and sufficient substrate availability. The review further discusses the relevance of animal-derived fermented foods as reservoirs of microbial biodiversity and emphasizes the potential of indigenous LAB strains from animal-origin products as natural sources of GABA. Understanding the biodiversity and functional traits of animal-associated LAB contributes not only to microbial ecology and wildlife-related microbiomes but also to the development of naturally derived functional foods with potential benefits for animal and human health.
References
Cho, Y. R., Chang, J. Y., & Chang, H. C. (2007). Production of gamma-aminobutyric acid (GABA) by Lactobacillus brevis OPK-3 isolated from kimchi. Korean Journal of Microbiology and Biotechnology, 35(4), 267–272.
De Biase, D., & Pennacchietti, E. (2012). Glutamate decarboxylase-dependent acid resistance in orally acquired bacteria: Function, distribution and biomedical implications of the gadBC operon. Molecular Microbiology, 86(4), 770–786. https://doi.org/10.1111/mmi.12020
Dhakal, R., Bajpai, V. K., & Baek, K. H. (2012). Production of gamma-aminobutyric acid (GABA) by microorganisms: A review. Brazilian Journal of Microbiology, 43(4), 1230–1241.
Diana, M., Quílez, J., & Rafecas, M. (2014). Gamma-aminobutyric acid as a bioactive compound in foods: A review. Journal of Functional Foods, 10, 407–420. https://doi.org/10.1016/j.jff.2014.07.004
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. https://doi.org/10.1111/jam.12011
Hiraga, K., Ueno, Y., & Oda, K. (2008). Glutamate decarboxylase from Lactobacillus brevis: Activation by ammonium sulfate. Bioscience, Biotechnology, and Biochemistry, 72(5), 1299–1306.
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 gamma-aminobutyric acid (GABA) in mild hypertensives. European Journal of Clinical Nutrition, 57(3), 490–495.
Komatsuzaki, N., Shima, J., Kawamoto, S., Momose, H., & Kimura, T. (2005). Production of gamma-aminobutyric acid (GABA) by Lactobacillus paracasei isolated from traditional fermented foods. Food Microbiology, 22(6), 497–504.
Li, H., & Cao, Y. (2010). Lactic acid bacterial cell factories for gamma-aminobutyric acid. Amino Acids, 39(5), 1107–1116. https://doi.org/10.1007/s00726-010-0582-7
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.
Lyu, C., Zhao, W., Peng, C., Hu, S., Fang, H., Hua, Y., et al. (2018). Exploration of the molecular basis of gamma-aminobutyric acid (GABA) production in Lactobacillus brevis for the manufacture of fermented GABA-enriched food. Journal of Agricultural and Food Chemistry, 66(10), 2561–2568.
Nomura, M., Kimoto, H., Someya, Y., & Suzuki, I. (1998). Production of gamma-aminobutyric acid by cheese starters during cheese ripening. Journal of Dairy Science, 81(6), 1486–1491.
Okada, T., Sugishita, T., Murakami, T., Murai, H., Saikusa, T., Horino, T., et al. (2000). Effect of defatted rice germ enriched with gamma-aminobutyric acid for sleeplessness, depression and autonomic disorder by oral administration. Nippon Shokuhin Kagaku Kogaku Kaishi, 47(8), 596–603.
Salminen, S., von Wright, A., & Ouwehand, A. (Eds.). (2004). Lactic acid bacteria: Microbiological and functional aspects (3rd ed.). Marcel Dekker.
Shi, F., & Li, Y. (2011). Synthesis of gamma-aminobutyric acid by expressing Lactobacillus brevis glutamate decarboxylase in Escherichia coli. Applied Biochemistry and Biotechnology, 164(8), 1377–1389.
Sun, L., Li, X., Zhang, Y., Yang, W., & Ma, G. (2019). A novel gamma-aminobutyric acid-producing Lactobacillus plantarum isolate as a potential probiotic for the treatment of anxiety. Journal of Functional Foods, 52, 216–223.
Villegas, J. M., Brown, L., Savoy de Giori, G., & Hebert, E. M. (2016). Optimization of batch culture conditions for GABA production by Lactobacillus brevis CRL 2013. Applied Microbiology and Biotechnology, 100(17), 7559–7567. https://doi.org/10.1007/s00253-016-7619-2
Wong, C. G., Bottiglieri, T., & Snead, O. C. (2003). GABA, gamma-hydroxybutyric acid, and neurological disease. Annals of Neurology, 54(S6), S3–S12.
Wu, Q., & Shah, N. P. (2017). High gamma-aminobutyric acid production from lactic acid bacteria: Emphasis on Lactobacillus brevis as a functional dairy starter. Critical Reviews in Food Science and Nutrition, 57(17), 3661–3672.
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