RT Journal Article
SR Electronic
T1 Identification of bacterial lipopeptides as key players in IBS
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP gutjnl-2022-328084
DO 10.1136/gutjnl-2022-328084
A1 Camille Petitfils
A1 Sarah Maurel
A1 Gaelle Payros
A1 Amandine Hueber
A1 Bahija Agaiz
A1 Géraldine Gazzo
A1 Rémi Marrocco
A1 Frédéric Auvray
A1 Geoffrey Langevin
A1 Jean-Paul Motta
A1 Pauline Floch
A1 Marie Tremblay-Franco
A1 Jean-Marie Galano
A1 Alexandre Guy
A1 Thierry Durand
A1 Simon Lachambre
A1 Anaëlle Durbec
A1 Hind Hussein
A1 Lisse Decraecker
A1 Justine Bertrand-Michel
A1 Abdelhadi Saoudi
A1 Eric Oswald
A1 Pierrick Poisbeau
A1 Gilles Dietrich
A1 Chloe Melchior
A1 Guy Boeckxstaens
A1 Matteo Serino
A1 Pauline Le Faouder
A1 Nicolas Cenac
YR 2022
UL http://gut.bmj.com/content/early/2022/10/14/gutjnl-2022-328084.abstract
AB 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 Prenatally stressed mice of both sexes presented visceral hypersensitivity, no overt colon inflammation or barrier dysfunction but a gut microbiota dysbiosis. The dysbiosis was distinguished by a decreased abundance of Ligilactobacillus murinus, 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.All data relevant to the study are included in the article or uploaded as supplementary information.