Immunomodulatory Properties of a γ-Aminobutyric Acid-Enriched Strawberry Juice Produced by Levilactobacillus brevis CRL 2013

Abstract

Gamma-aminobutyric acid (GABA) plays a key role in mammals as the major inhibitory neurotransmitter of the central nervous system. Although GABA may not be able to cross the human blood-brain barrier, it was approved as a food ingredient because of its benefits to the host after oral administration including anti-hypertensive, anti-depressant and anti-inflammatory activities. Considering the current trend toward the development of new functional and natural products and that microbial fermentation is one of the most promising methods to produce this non-protein amino acid, the in situ production of GABA through fermentation of strawberry and blueberry juices by the efficient GABA producer strain, Levilactobacillus brevis (formerly known as Lactobacillus brevis) CRL 2013, was evaluated. A high GABA production (262 mM GABA) was obtained after fermenting strawberry juice supplemented with yeast extract for 168 h, being GABA yield significantly higher in strawberry juices than in the blueberry ones. Thus, GABA-enriched fermented strawberry juice (FSJ) was selected to carry out in vivo and in vitro studies. The in vitro functional analysis of the GABA-enriched FSJ demonstrated its ability to significantly decrease the expression of cox-2 gene in LPS stimulated RAW 264.7 macrophages. In addition, in vivo studies in mice demonstrated that both, L. brevis CRL 2013 and the GABA-enriched FSJ were capable of reducing the levels of peritoneal, intestinal and serum TNF-α, IL-6, and CXCL1, and increasing IL-10 and IFN-γ in mice exposed to an intraperitoneal challenge of LPS. Of note, the GABA-enriched FSJ was more efficient than the CRL 2013 strain to reduce the pro-inflammatory factors and enhance IL-10 production. These results indicated that the CRL 2013 strain exerts anti-inflammatory effects in the context of LPS stimulation and that this effect is potentiated by fermentation. Our results support the potential use of L. brevis CRL 2013 as an immunomodulatory starter culture and strawberry juice as a remarkable vegetable matrix for the manufacture of GABA-enriched fermented functional foods capable of differentially modulating the inflammatory response triggered by TLR4 activation.

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“…The reactions occurred with 40 µL of supernatant 108 µL of Tris/HCl buffer (160 mM (Sigma)), 6.6 µL of 2-mercaptoethanol (100 mM (Sigma)), 10 µL of α-cetoglutarato (100 mM (Sigma)), 10 µL of NADP (25 mM (Sigma)), 5.5 µL of ultrapurewater and 20 µL of GABase (Sigma). The absorbance was measured at 340 nm every 15 s for 5 min in the centering of plates with 96 cups and results were expressed as mM of the GABA [ 49 ].…”

The Application and Optimization of HIPEF Technology in the Processing of Juice from Strawberries Harvested at Two Stages of Ripeness

“…For example, Zhao et al investigated the antioxidant and antibacterial potential of functional strawberry juice inoculated with a starter culture of lactic acid bacteria (LAB) and yeasts [ 8 ]. A similar methodology was used by Cataldo et al in their work in which strawberry juice was inoculated with Levilactobacillus brevis to study the immunomodulatory effect of gamma-aminobutyric acid on rodent cell cultures [ 9 ]. In addition to processing into juice, studies have also shown the potential of processing strawberries into dry powders [ 10 ].…”

The anti-inflammatory activity of GABA-enriched Moringa oleifera leaves produced by fermentation with Lactobacillus plantarum LK-1

“…Gamma-aminobutyric acid (GABA) is a non-protein amino acid that can be found in plants, bacteria and animals ( 5 ). It's an important inhibitory neurotransmitter that presented in mammal central nervous system with multiple physiological functions including anti-inflammation ( 6 ). For example, GABA showed obvious anti-inflammatory effect on streptozotocin-treated mice by decreasing the synthesis of inflammatory mediators like IL-1β, TNF-α, IFN-γ, IL-12, and increasing the production of anti-inflammatory mediator TGF-β1 ( 7 ).…”

“…Besides, GABA restrained the expression of inflammatory cytokines (L-6, IL8, and TNF-α) and alleviated inflammatory response of MAC-T cells induced by LPS via the TLR4-MyD88-NFκB signaling pathway ( 8 ). Except for anti-inflammation, GABA has also been reported to possess hypotensive, antidiabetic, immunity enhancement, and sedative effects, and has been applied to alleviate sleeplessness, depression and improve visual cortical function ( 6 , 9 ). Despite its various physiological functions, GABA content in natural animal- and plant-based food products is pretty low which cannot meet people's needs ( 6 ).…”