Conditioned media from gamma-aminobutyric acid (GABA)-producing Lactobacillus brevis influences enteric nerve activity and displays a similar bioactivity and pharmacological profile as GABA ex vivo
Kevin W. Lomasney1,2, John F. Cryan1,3, Niall P.Hyland1,2
APC Microbiome Institute 1 and Departments of Pharmacology & Therapeutics 2 and Anatomy & Neuroscience 3, University College Cork, Cork, Ireland
Lactic acid bacteria have been described as “cell factories” for gamma-aminobutyric acid (GABA; Li & Cao, 2012) and thus have potential as delivery vehicles for GABA to the intestine.
A screen of human-derived bacteria identified five efficient GABA-producing strains (Barret et al., 2012). Of these, we selected a Lactobacillus with the greatest GABA production to prepare GABA-enriched media. GABA and its receptors are widely expressed in the gastrointestinal tract (GI), including on enteric neurones, where they regulate physiological functions.
Therefore, we examined the effects of conditioned media (CM) from Lactobacillus brevis and GABA on colonic physiology in Ussing chambers and further characterised the nature of these effects using the GABAA receptor antagonist, bicuculline, the GABAB receptor antagonist, phaclofen and the neurotoxin, tetrodotoxin (TTx) in colonic mucosa-submucosa preparations.
CM from a GABA-producing Lactobacillus significantly increased baseline Isc relative to CM from a non GABA-producing isolate. In contrast, GABA had no significant effect on baseline Isc. CM, in a similar manner to GABA, significantly inhibited cholinergic-induced colonic ion transport relative to that from a non GABA-producer. This effect was sensitive to GABAA receptor antagonism. Moreover, the TTx sensitivity of these responses suggests that the GABAA receptor-mediated effect most likely involves the enteric nervous system.
Factors derived from Lactobacillus brevis selectively activate enteric GABAA receptors and regulate colonic secretory function in a similar manner to GABA. These data suggest that GABA-producing microbes may be useful tools in modulating GABAA receptor-mediated functions in the colon.