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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  Lactococcus lactis  and one mutant were characterized  in vitro  for their GABA production and tested  in vivo  in rat by oral gavage for their antinociceptive properties.  L. lactis  NCDO2118 significantly reduced visceral hypersensitivity induced by stress due to its glutamate decarboxylase (GAD) activity.  L. lactis  NCDO2727 with similar genes for GABA metabolism but no detectable GAD activity had no  in vivo  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  L. lactis  NCDO2118 treatment. These findings reveal the crucial role of the microbial GAD activity of  L. lactis  NCDO2118 to deliver GABA into the gastro-intestinal tract for exerting antinociceptive properties  in vivo  and open avenues for this GRAS (Generally Recognized As safe) bacterium in the management of visceral pain and anxious profile of IBS patients.

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