Lactococcus lactis CNCM I‐5388 versus NCDO2118 by its GABA hyperproduction ability, counteracts faster stress‐induced intestinal hypersensitivity in rats

Pedro Gomes (1, 2) , Valérie Laroute (1) , Catherine Beaufrand (3) , Marie-Line Daveran Mingot (1) , Nathalie Aubry (1) , Chloé Liebgott (2) , Nathalie Ballet (4) , Sophie Legrain-Raspaud (5) , Vassilia Théodorou (3) , Muriel Mercier-Bonin (2) , Muriel Cocaign-Bousquet (1) , Hélène Eutamène (3)

1 TBI - Toulouse Biotechnology Institute
2 ToxAlim - ToxAlim
3 ToxAlim-NGN - Neuro-Gastroentérologie & Nutrition
4 Lesaffre
5 Groupe DANONE

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by its main symptom, visceral hypersensitivity (VH), which is aggravated by stress. Gut–brain interactions and gut bacteria may alleviate IBS symptoms, including VH. γ‐amino butyric acid (GABA), produced notably by lactic acid bacteria (LAB), shows promising result in IBS symptoms treatment. In bacteria, GABA is generated through glutamate decarboxylase (GAD) metabolism of L‐glutamic acid, maintaining intracellular pH. In mammals, GABA acts as an inhibitory neurotransmitter, modulating pain, stress, and anxiety. Therefore, utilizing GABA‐producing LAB as a therapeutic approach might be beneficial. Our previous work showed that a GABA‐producing Lactococcus lactis strain, NCDO2118, reduced VH induced by acute stress in rats after a 10‐day oral treatment. Here, we identified the strain CNCM I‐5388, with a four‐fold higher GABA production rate under the same conditions as NCDO2118. Both strains shared 99.1% identical GAD amino acid sequences and in vitro analyses revealed the same optimal pH for GAD activity; however, CNCM I‐5388 exhibited 17 times higher intracellular GAD activity and increased resistance to acidic pH. Additionally, in vivo experiments have demonstrated that CNCM I‐5388 has faster anti‐VH properties in rats compared with NCDO2118, starting from the fifth day of treatment. Finally, CNCM I‐5388 anti‐VH effects partially persisted after 5‐day treatment interruption and after a single oral treatment. These findings highlight CNCM I‐5388 as a potential therapeutic agent for managing VH in IBS patients.

Mots clés: Lactococcus lactis; GABA; GAD activity; psychological acute stress; visceral hypersensitivity

Domaines: Sciences du Vivant [q-bio]

Pedro Gomes, Valérie Laroute, Catherine Beaufrand, Marie-Line Daveran Mingot, Nathalie Aubry, et al.. Lactococcus lactis CNCM I‐5388 versus NCDO2118 by its GABA hyperproduction ability, counteracts faster stress‐induced intestinal hypersensitivity in rats. FASEB Journal, 2023, 37 (11), pp.e23264. ⟨10.1096/fj.202301588R⟩. ⟨hal-04388025⟩