摘要Background Intestinal barrier is a dynamic interface between the body and the ingested food components,how-ever,dietary components or xenobiotics could compromise intestinal integrity,causing health risks to the host.Gossypol,a toxic component in cottonseed meal(CSM),caused intestinal injury in fish or other monogastric animals.It has been demonstrated that probiotics administration benefits the intestinal barrier integrity,but the efficacy of probiotics in maintaining intestinal health when the host is exposed to gossypol remains unclear.Here,a strain(YC)affiliated to Pediococcus pentosaceus was isolated from the gut of Nile tilapia(Oreochromis niloticus)and its potential to repair gossypol-induced intestinal damage was evaluated.Results A total of 270 Nile tilapia(2.20±0.02 g)were allotted in 3 groups with 3 tanks each and fed with 3 diets including CON(control diet),GOS(control diet containing 300mg/kg gossypol)and GP(control diet containing 300mg/kg gossypol and 108colony-forming unit(CFU)/g P.pentosaceus YC),respectively.After 10weeks,addition of P.pentosaceus YC restored growth retardation and intestinal injury induced by gossypol in Nile tilapia.Transcriptome analysis and siRNA interference experiments demonstrated that NOD-like receptors(NLR)family caspase recruitment domain(CARD)domain containing 3(Nlrc3)inhibition might promote intestinal stem cell(ISC)proliferation,as well as maintaining gut barrier integrity.16S rRNA sequencing and gas chromatography-mass spectrometry(GC-MS)revealed that addition of P.pentosaceus YC altered the composition of gut microbiota and increased the content of propionate in fish gut.In vitro studies on propionate's function demonstrated that it suppressed nlrc3 expression and promoted wound healing in Caco-2 cell model.Conclusions The present study reveals that P.pentosaceus YC has the capacity to ameliorate intestinal barrier injury by modulating gut microbiota composition and elevating propionate level.This finding offers a promising strategy for the feed industry to incorporate cottonseed meal into fish feed formulations.