{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T14:59:34Z","timestamp":1791644374148,"version":"4.3.4"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T00:00:00Z","timestamp":1637798400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012659","name":"Foundation for Innovative Research Groups of the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No.31672435"],"award-info":[{"award-number":["No.31672435"]}],"id":[{"id":"10.13039\/501100012659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Vasoactive intestinal peptide (VIP) plays an important role in the neuro-endocrine-immune system. Mast cells (MCs) are important immune effector cells. This study was conducted to investigate the protective effect of <jats:italic>L. casei<\/jats:italic> ATCC 393 on Enterotoxigenic <jats:italic>Escherichia coli<\/jats:italic> (ETEC) K88-induced intestinal mucosal immune barrier injury and its association with VIP\/MC signaling by <jats:italic>in vitro<\/jats:italic> experiments in cultures of porcine mucosal mast cells (PMMCs) and <jats:italic>in vivo<\/jats:italic> experiments using VIP receptor antagonist (aVIP) drug. The results showed that compared with the ETEC K88 and lipopolysaccharides (LPS)-induced model groups, VIP pretreatment significantly inhibited the activation of MCs and the release of \u03b2-hexosaminidase (\u03b2-hex), histamine and tryptase. Pretreatment with aVIP abolished the protective effect of <jats:italic>L. casei<\/jats:italic> ATCC 393 on ETEC K88-induced intestinal mucosal immune barrier dysfunction in C57BL\/6 mice. Also, with the blocking of VIP signal transduction, the ETEC K88 infection increased serum inflammatory cytokines, and the numbers of degranulated MCs in ileum, which were decreased by administration of <jats:italic>L. casei<\/jats:italic> ATCC 393. In addition, VIP mediated the regulatory effect of <jats:italic>L. casei<\/jats:italic> ATCC 393 on intestinal microbiota in mice. These findings suggested that VIP may mediate the protective effect of <jats:italic>L.casei<\/jats:italic> ATCC 393 on intestinal mucosal immune barrier dysfunction <jats:italic>via<\/jats:italic> MCs.<\/jats:p>","DOI":"10.3389\/fimmu.2021.723173","type":"journal-article","created":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T03:00:31Z","timestamp":1638327631000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["The Role of Vasoactive Intestinal Peptide and Mast Cells in the Regulatory Effect of Lactobacillus casei ATCC 393 on Intestinal Mucosal Immune Barrier"],"prefix":"10.3389","volume":"12","author":[{"given":"Xiaofan","family":"Song","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanyao","family":"Pi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueming","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengxia","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuqi","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Qiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xina","family":"Dou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongyan","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunlan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.12717","article-title":"The Joint Power of Sex and Stress to Modulate Brain-Gut-Microbiota Axis and Intestinal Barrier Homeostasis: Implications for Irritable Bowel Syndrome","volume":"28","author":"Pigrau","year":"2016","journal-title":"Neurogastroenterol Motil"},{"key":"B2","doi-asserted-by":"publisher","first-page":"988","DOI":"10.3390\/nu10080988","article-title":"The Potential of Gut Commensals in Reinforcing Intestinal Barrier Function and Alleviating Inflammation","volume":"10","author":"Hiippala","year":"2018","journal-title":"Nutrients"},{"key":"B3","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1017\/S0007114516004037","article-title":"Can Probiotics Modulate Human Disease by Impacting Intestinal Barrier Function","volume":"117","author":"Bron","year":"2017","journal-title":"Br J Nutr"},{"key":"B4","doi-asserted-by":"publisher","first-page":"195","DOI":"10.14309\/ajg.0000000000000504","article-title":"Small Intestinal Bacterial Overgrowth in Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis of Case-Control Studies","volume":"115","author":"Shah","year":"2020","journal-title":"Am J Gastroenterol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1600240","DOI":"10.1002\/mnfr.201600240","article-title":"Probiotics, Gut Microbiota, and Their Influence on Host Health and Disease","volume":"61","author":"Sanchez","year":"2017","journal-title":"Mol Nutr Food Res"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.copbio.2005.02.003","article-title":"Probiotic and Other Functional Microbes: From Markets to Mechanisms","volume":"16","author":"Saxelin","year":"2005","journal-title":"Curr Opin Biotechnol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1080\/10408390903551747","article-title":"Evidence Supporting the Use of Probiotics for the Prevention and Treatment of Chemotherapy-Induced Intestinal Mucositis","volume":"51","author":"Prisciandaro","year":"2011","journal-title":"Crit Rev Food Sci Nutr"},{"key":"B8","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/1475-2891-6-17","article-title":"The Role of a Probiotics Mixture in the Treatment of Childhood Constipation: A Pilot Study","volume":"6","author":"Bekkali","year":"2007","journal-title":"Nutr J"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.20736","article-title":"Lactobacillus Casei Downregulates Commensals' Inflammatory Signals in Crohn's Disease Mucosa","volume":"15","author":"Llopis","year":"2009","journal-title":"Inflammation Bowel Dis"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.01360-15","article-title":"Attenuation of Colitis by Lactobacillus Casei BL23 Is Dependent on the Dairy Delivery Matrix","volume":"81","author":"Lee","year":"2015","journal-title":"Appl Environ Microbiol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"e0156374","DOI":"10.1371\/journal.pone.0156374","article-title":"The Impact of Lactobacillus Casei on the Composition of the Cecal Microbiota and Innate Immune System Is Strain Specific","volume":"11","author":"Aktas","year":"2016","journal-title":"PLoS One"},{"key":"B12","doi-asserted-by":"publisher","first-page":"e0145784","DOI":"10.1371\/journal.pone.0145784","article-title":"The Effect of Lactobacillus Casei 32G on the Mouse Cecum Microbiota and Innate Immune Response Is Dose and Time Dependent","volume":"10","author":"Aktas","year":"2015","journal-title":"PLoS One"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1111\/1751-7915.13407","article-title":"Lactobacillus Casei Expressing Internalins A and B Reduces Listeria Monocytogenes Interaction With Caco-2 Cells In Vitro","volume":"12","author":"Mathipa","year":"2019","journal-title":"Microb Biotechnol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"117281","DOI":"10.1016\/j.lfs.2020.117281","article-title":"Lactobacillus Casei ATCC 393 Alleviates Enterotoxigenic Escherichia Coli K88-Induced Intestinal Barrier Dysfunction via TLRs\/mast Cells Pathway","volume":"244","author":"Xu","year":"2020","journal-title":"Life Sci"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00620","article-title":"Mast Cell: A Multi-Functional Master Cell","volume":"6","author":"Krystel-Whittemore","year":"2015","journal-title":"Front Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1136\/gut.48.5.630","article-title":"Role of Mast Cells in Chronic Stress Induced Colonic Epithelial Barrier Dysfunction in the Rat","volume":"48","author":"Santos","year":"2001","journal-title":"Gut"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-020-01376-4","article-title":"A Role for Mast Cells and Mast Cell Tryptase in Driving Neutrophil Recruitment in LPS-Induced Lung Inflammation via Protease-Activated Receptor 2 in Mice","volume":"69","author":"de Almeida","year":"2020","journal-title":"Inflamm Res"},{"key":"B18","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1369\/0022155414545334","article-title":"Mast Cell Function: A New Vision of an Old Cell","volume":"62","author":"Marcelino da Silva","year":"2014","journal-title":"J Histochem Cytochem"},{"key":"B19","doi-asserted-by":"publisher","first-page":"135","DOI":"10.3390\/cells8020135","article-title":"Intestinal Mucosal Mast Cells: Key Modulators of Barrier Function and Homeostasis","volume":"8","author":"Albert-Bayo","year":"2019","journal-title":"Cells"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.90551.2008","article-title":"Vasoactive Intestinal Peptide Ameliorates Intestinal Barrier Disruption Associated With Citrobacter Rodentium-Induced Colitis","volume":"297","author":"Conlin","year":"2009","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.12127","article-title":"Vasoactive Intestinal Polypeptide Regulates Barrier Function via Mast Cells in Human Intestinal Follicle-Associated Epithelium and During Stress in Rats","volume":"25","author":"Keita","year":"2013","journal-title":"Neurogastroenterol Motil"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1159\/000165352","article-title":"Correlation of Gut Hormones With Irritable Bowel Syndrome","volume":"78","author":"Zhang","year":"2008","journal-title":"Digestion"},{"key":"B23","doi-asserted-by":"publisher","first-page":"152230","DOI":"10.1016\/j.tox.2019.06.001","article-title":"T-2 Toxin Inhibits the Production of Mucin via Activating the IRE1\/XBP1 Pathway","volume":"424","author":"Lin","year":"2019","journal-title":"Toxicology"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.193482","article-title":"The Mucosal Barrier at a Glance","volume":"130","author":"France","year":"2017","journal-title":"J Cell Sci"},{"key":"B25","doi-asserted-by":"publisher","first-page":"100938","DOI":"10.1016\/j.arr.2019.100938","article-title":"Intestinal Epithelial Barrier Functions in Ageing","volume":"54","author":"Branca","year":"2019","journal-title":"Ageing Res Rev"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.jff.2018.05.029","article-title":"Probiotics in IBD: Combining In Vitro and In Vivo Models for Selecting Strains With Both Anti-Inflammatory Potential as Well as a Capacity to Restore the Gut Epithelial Barrier","volume":"47","author":"Zaylaa","year":"2018","journal-title":"J Funct Foods"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.livres.2020.03.002","article-title":"Intestinal Barrier Function and Metabolic\/Liver Diseases","volume":"4","author":"Ghosh","year":"2020","journal-title":"Liver Res"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.burns.2019.07.007","article-title":"The Role of Thermal Injury on Intestinal Bacterial Translocation and the Mitigating Role of Probiotics: A Review of Animal and Human Studies","volume":"46","author":"Knackstedt","year":"2020","journal-title":"Burns"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.lwt.2016.08.021","article-title":"Interaction Between Putative Probiotic Lactobacillus Strains of Indian Gut Origin and Salmonella: Impact on Intestinal Barrier Function","volume":"84","author":"Rokana","year":"2017","journal-title":"Lwt"},{"key":"B30","doi-asserted-by":"publisher","first-page":"117089","DOI":"10.1016\/j.lfs.2019.117089","article-title":"Probiotic Mixtures With Aerobic Constituent Promoted the Recovery of Multi-Barriers in DSS-Induced Chronic Colitis","volume":"240","author":"Chen","year":"2019","journal-title":"Life Sci"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2015.02.008","article-title":"Mast Cell Activation Disease and Microbiotic Interactions","volume":"37","author":"Afrin","year":"2015","journal-title":"Clin Ther"},{"key":"B32","doi-asserted-by":"publisher","first-page":"173035","DOI":"10.1016\/j.ejphar.2020.173035","article-title":"Microglia and Mast Cells Generate Proinflammatory Cytokines in the Brain and Worsen Inflammatory State: Suppressor Effect of IL-37","volume":"875","author":"Conti","year":"2020","journal-title":"Eur J Pharmacol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1007\/978-1-4939-0897-4_4","article-title":"Intestinal Barrier Function and the Brain-Gut Axis","volume":"817","author":"Alonso","year":"2014","journal-title":"Adv Exp Med Biol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2015-309151","article-title":"The Role of Mast Cells in Functional GI Disorders","volume":"65","author":"Wouters","year":"2016","journal-title":"Gut"},{"key":"B35","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.bbadis.2010.12.014","article-title":"Mast Cells and Inflammation","volume":"1822","author":"Theoharides","year":"2012","journal-title":"Biochim Biophys Acta"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpedsurg.2019.08.038","article-title":"Vasoactive Intestinal Peptide Decreases Inflammation and Tight Junction Disruption in Experimental Necrotizing Enterocolitis","volume":"54","author":"Seo","year":"2019","journal-title":"J Pediatr Surg"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2011.01.001","article-title":"VPAC1 (Vasoactive Intestinal Peptide (VIP) Receptor Type 1) G Protein-Coupled Receptor Mediation of VIP Enhancement of Murine Experimental Colitis","volume":"267","author":"Yadav","year":"2011","journal-title":"Cell Immunol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2004.12.019","article-title":"Brain Mast Cells and Therapeutic Potential of Vasoactive Intestinal Peptide in a Parkinson's Disease Model in Rats: Brain Microdialysis, Behavior, and Microscopy","volume":"26","author":"Tuncel","year":"2005","journal-title":"Peptides"},{"key":"B39","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.urology.2003.08.010","article-title":"Protective Effect of Vasoactive Intestinal Peptide on Testicular Torsion-Detorsion Injury: Association With Heparin-Containing Mast Cells","volume":"63","author":"Can","year":"2004","journal-title":"Urology"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/S0196-9781(99)00177-1","article-title":"Vasoactive Intestinal Peptide Inhibits Degranulation and Changes Granular Content of Mast Cells: A Potential Therapeutic Strategy in Controlling Septic Shock","volume":"21","author":"Tuncel","year":"2000","journal-title":"Peptides"},{"key":"B41","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/S0065-2776(07)95006-3","article-title":"Mast Cell Proteases","volume":"95","author":"Pejler","year":"2007","journal-title":"Adv Immunol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.2174\/1389203716666150630134356","article-title":"Crosstalk Between the Immune Receptors and Gut Microbiota","volume":"16","author":"Mu","year":"2015","journal-title":"Curr Protein Pept Sci"},{"key":"B43","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1007\/978-1-4939-0897-4_9","article-title":"Neuropeptides and the Microbiota-Gut-Brain Axis","volume":"817","author":"Holzer","year":"2014","journal-title":"Adv Exp Med Biol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00323.2003","article-title":"Toll-Like Receptors: Function and Roles in Lung Disease","volume":"286","author":"Basu","year":"2004","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/nri1900","article-title":"IRFs: Master Regulators of Signalling by Toll-Like Receptors and Cytosolic Pattern-Recognition Receptors","volume":"6","author":"Honda","year":"2006","journal-title":"Nat Rev Immunol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.aninu.2020.09.002","article-title":"Interplay Between Gut Microbiota and Antimicrobial Peptides","volume":"6","author":"Zong","year":"2020","journal-title":"Anim Nutr"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v17.i6.750","article-title":"Probiotic Lactobacillus Rhamnosus Downregulates FCER1 and HRH4 Expression in Human Mast Cells","volume":"17","author":"Oksaharju","year":"2011","journal-title":"World J Gastroenterol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00195.2014","article-title":"Vasoactive Intestinal Peptide Prevents Pkc\u03f5-Induced Intestinal Epithelial Barrier Disruption During EPEC Infection","volume":"308","author":"Morampudi","year":"2015","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00066.2003","article-title":"Human ENS Regulates the Intestinal Epithelial Barrier Permeability and a Tight Junction-Associated Protein ZO-1 via VIPergic Pathways","volume":"285","author":"Neunlist","year":"2003","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1038\/icb.1996.45","article-title":"The Effects of Four Neuropeptides on the Degranulation of Mucosal Mast Cells From Sheep","volume":"74","author":"Stewart","year":"1996","journal-title":"Immunol Cell Biol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.723173\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T03:00:33Z","timestamp":1638327633000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.723173\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,25]]},"references-count":50,"alternative-id":["10.3389\/fimmu.2021.723173"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.723173","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,25]]},"article-number":"723173"}}