Background: Irritable bowel syndrome (IBS) is a common disorder worldwide. It is characterized by abdominal pain/discomfort and changes in bowel habits. Due to themultifactorialpathophysiologyandtheheterogeneityofIBSpatients,appropriate treatment of IBS is still a challenge. Spascupreel (SP-11), as a multicomponent medication,hasthepotentialtomodulatemultiplepathophysiologicalpathwayssimultaneously.Therefore,theobjectiveofthecurrentstudywastoinvestigatethe effectsoforalSP-11treatmentonstress-inducedchangesofperipheralandcentral functionsinaratmodelmimickinghumanIBS. Methods: NaïveWistarratsweretreatedwithSP-11(0.9tab/kg)orNaCl0.9%by oralgavagefor4daysbefore2-hourpartialrestraintstress(PRS)procedure.Twenty minutesafterPRS,centralandperipheralstress-inducedchangesaffectingIBSwere assessed. These include the hypothalamic-pituitary-adrenal (HPA) axis response throughplasmaACTHandcorticosteronemeasurements,visceralpaininresponse tocolorectaldistension,gutpermeability,colonicmastcellnumber,andsensitization as well as gut transit time. Results: TreatmentwithSP-11reducedtheHPAaxisactivationinresponsetoPRS. At the gut level, a reduction in colonic hypersensitivity to colorectal distension, a normalizationofguttransittimeacceleration,areducedmastcellsensitization,anda trend toward reduced gut hyperpermeability were observed. Conclusions: Thesedatasuggestthatstress-inducedIBSsignscanbereducedusing SP-11inrats.TheobservedeffectsandthegoodtolerabilityofthedrugmakeSP-11 aninnovativecandidateinthemanagementofIBS. K E Y W O R D S gut-brainaxis,irritablebowelsyndrome,multicomponentmedication,partialrestraintstress, Spascupreel,SP-11 How to cite this article:TheodorouV,BeaufrandC,YvonS,et al. The multicomponent medication Spascupreel attenuates stress-inducedgutdysfunctioninrats.Neurogastroenterol