Lactococcus lactis NCDO2118 exerts visceral antinociceptive properties in rat via GABA production in the gastro-intestinal tract

Abstract

Gut disorders associated to irritable bowel syndrome (IBS) are combined with anxiety and depression. Evidence suggests that microbially produced neuroactive molecules, like γ-aminobutyric acid (GABA), can modulate the gut-brain axis. Two natural strains of <i>Lactococcus lactis</i> and one mutant were characterized <i>in vitro</i> for their GABA production and tested <i>in vivo</i> in rat by oral gavage for their antinociceptive properties. <i>L. lactis</i> NCDO2118 significantly reduced visceral hypersensitivity induced by stress due to its glutamate decarboxylase (GAD) activity. <i>L. lactis</i> NCDO2727 with similar genes for GABA metabolism but no detectable GAD activity had no <i>in vivo</i> effect, as well as the NCDO2118 ΔgadB mutant. The antinociceptive effect observed for the NCDO2118 strain was mediated by the production of GABA in the gastro-intestinal tract and blocked by GABA_B receptor antagonist. Only minor changes in the faecal microbiota composition were observed after the <i>L. lactis</i> NCDO2118 treatment. These findings reveal the crucial role of the microbial GAD activity of <i>L. lactis</i> NCDO2118 to deliver GABA into the gastro-intestinal tract for exerting antinociceptive properties <i>in vivo</i> and open avenues for this GRAS (Generally Recognized As safe) bacterium in the management of visceral pain and anxious profile of IBS patients.