Identification of bacterial lipopeptides as key players in IBS
Camille Petitfils, Sarah Maurel, Gaëlle Payros, Amandine Hueber, Bahija Agaiz, Géraldine Gazzo, Rémi Marrocco, Frédéric Auvray, Geoffrey Langevin, Jean‐Paul Motta, Pauline Floch, Marie Tremblay‐Franco, Jean‐Marie Galano, Alexandre Guy, Thierry Durand, Simon Lachambre, Anaëlle Durbec, Hind Hussein, Lisse Decraecker, Justine Bertrand‐Michel, Abdelhadi Saoudi, Éric Oswald, Pierrick Poisbeau, Gilles Dietrich, Chloé Melchior, Guy E. Boeckxstaens, Matteo Sérino, Pauline Le Faouder, Nicolas Cénac
Abstract
OBJECTIVES: Clinical studies revealed that early-life adverse events contribute to the development of IBS in adulthood. The aim of our study was to investigate the relationship between prenatal stress (PS), gut microbiota and visceral hypersensitivity with a focus on bacterial lipopeptides containing γ-aminobutyric acid (GABA). DESIGN: We developed a model of PS in mice and evaluated, in adult offspring, visceral hypersensitivity to colorectal distension (CRD), colon inflammation, barrier function and gut microbiota taxonomy. We quantified the production of lipopeptides containing GABA by mass spectrometry in a specific strain of bacteria decreased in PS, in PS mouse colons, and in faeces of patients with IBS and healthy volunteers (HVs). Finally, we assessed their effect on PS-induced visceral hypersensitivity. RESULTS: , in both sexes, inversely correlated with visceral hypersensitivity to CRD in mice. An isolate from this bacterial species produced several lipopeptides containing GABA including C14AsnGABA. Interestingly, intracolonic treatment with C14AsnGABA decreased the visceral sensitivity of PS mice to CRD. The concentration of C16LeuGABA, a lipopeptide which inhibited sensory neurons activation, was decreased in faeces of patients with IBS compared with HVs. CONCLUSION: PS impacts the gut microbiota composition and metabolic function in adulthood. The reduced capacity of the gut microbiota to produce GABA lipopeptides could be one of the mechanisms linking PS and visceral hypersensitivity in adulthood.