{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T15:46:29Z","timestamp":1748447189595,"version":"3.40.5"},"reference-count":28,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T00:00:00Z","timestamp":1676937600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science & ICT","award":["NRF-2012M3A9C4048761"],"award-info":[{"award-number":["NRF-2012M3A9C4048761"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>It is crucial for human health that the immune system of the gastrointestinal tract works effectively. Dietary modulation is one of the factors that regulate the immune response in the gut. This study aims to develop a safe human challenge model to study gastrointestinal inflammation and immune function. This study focuses on evaluating gut stimulation induced by the oral cholera vaccine in healthy people. In addition, this paper describes the study design for assessing the efficacy and safety of a probiotic lysate, identifying whether functional ingredients in food can modulate inflammatory response induced by oral cholera vaccine. Forty-six males aged 20 to 50 with healthy bowel habits will be randomly allocated to the placebo or intervention group. Participants will consume 1 capsule of probiotic lysate or placebo twice daily for 6 weeks, take oral cholera vaccines on visit 2 (day 15) and visit 5 (day 29). The level of fecal calprotectin, a marker of gut inflammation, will be the primary outcome. The changes of cholera toxin-specific antibody levels and local\/systemic inflammatory responses will be evaluated in blood. The purpose of this study is to evaluate gut stimulation of the oral cholera vaccine and investigate the effect of a probiotic lysate on improving the mild inflammatory response induced by the vaccine or supporting the immune response in healthy subjects.<\/jats:p>\n<jats:p><jats:bold>Trial registration<\/jats:bold>: * This trial is registered in the International Clinical Trials Registry Platform of WHO (ICTRP, registration number: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/trialsearch.who.int\/Trial2.aspx?TrialID=KCT0002589\" xlink:type=\"simple\">KCT0002589<\/jats:ext-link>).<\/jats:p>","DOI":"10.1371\/journal.pone.0281817","type":"journal-article","created":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T01:52:01Z","timestamp":1677030721000},"page":"e0281817","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Study protocol for cholera vaccination as a model to measure the inflammatory response in the gut: A case of modulation with a Lactobacillus plantarum K8 lysate"],"prefix":"10.1371","volume":"18","author":[{"given":"Min Young","family":"Park","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soo-yeon","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anita","family":"Hartog","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Els","family":"van Hoffen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alwine","family":"Kardinaal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joohee","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hee Jung","family":"Choi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oran","family":"Kwon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4316-2726","authenticated-orcid":true,"given":"Ji Yeon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,2,21]]},"reference":[{"issue":"3","key":"pone.0281817.ref001","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1079\/BJN20051469","article-title":"Markers to measure immunomodulation in human nutrition intervention studies","volume":"94","author":"R Albers","year":"2005","journal-title":"British Journal of Nutrition"},{"issue":"4","key":"pone.0281817.ref002","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.2903\/j.efsa.2011.1984","article-title":"Guidance on the scientific requirements for health claims related to gut and immune function","volume":"9","author":"EFSA Panel on Dietetic Products N, Allergies","year":"2011","journal-title":"EFSA Journal"},{"issue":"S1","key":"pone.0281817.ref003","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1017\/S0007114512005119","article-title":"A consideration of biomarkers to be used for evaluation of inflammation in human nutritional studies","volume":"109","author":"PC Calder","year":"2013","journal-title":"British Journal of Nutrition"},{"issue":"3","key":"pone.0281817.ref004","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1017\/S0007114513002547","article-title":"Lactobacillus acidophilus supplementation in human subjects and their resistance to enterotoxigenic Escherichia coli infection","volume":"111","author":"A Ouwehand","year":"2014","journal-title":"British journal of nutrition"},{"issue":"3","key":"pone.0281817.ref005","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1038\/ejcn.2014.238","article-title":"The effect of a multi-strain probiotic on the resistance toward Escherichia coli challenge in a randomized, placebo-controlled, double-blind intervention study","volume":"69","author":"S Ten Bruggencate","year":"2015","journal-title":"European journal of clinical nutrition"},{"issue":"5822","key":"pone.0281817.ref006","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1038\/292413a0","article-title":"Actions of cholera toxin and the prevention and treatment of cholera","volume":"292","author":"J. Holmgren","year":"1981","journal-title":"Nature"},{"issue":"6","key":"pone.0281817.ref007","doi-asserted-by":"crossref","first-page":"2884","DOI":"10.1128\/IAI.67.6.2884-2890.1999","article-title":"Antibody responses in the lower respiratory tract and male urogenital tract in humans after nasal and oral vaccination with cholera toxin B subunit","volume":"67","author":"A Rudin","year":"1999","journal-title":"Infection and immunity"},{"key":"pone.0281817.ref008","unstructured":"Health functional food code (No. 2020\u201392). Korea Food and Drug Administration."},{"issue":"1","key":"pone.0281817.ref009","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.tim.2011.09.004","article-title":"Anti-inflammatory potential of probiotics: lipoteichoic acid makes a difference","volume":"20","author":"S Lebeer","year":"2012","journal-title":"Trends in microbiology"},{"issue":"1","key":"pone.0281817.ref010","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.intimp.2008.10.014","article-title":"Differential immunostimulatory effects of Gram-positive bacteria due to their lipoteichoic acids","volume":"9","author":"YH Ryu","year":"2009","journal-title":"International immunopharmacology"},{"issue":"4","key":"pone.0281817.ref011","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.molimm.2010.07.011","article-title":"Lactobacillus plantarum lipoteichoic acid down-regulated Shigella flexneri peptidoglycan-induced inflammation","volume":"48","author":"HG Kim","year":"2011","journal-title":"Molecular immunology"},{"issue":"15\u201316","key":"pone.0281817.ref012","doi-asserted-by":"crossref","first-page":"2170","DOI":"10.1016\/j.molimm.2011.07.009","article-title":"Lipoteichoic acid from Lactobacillus plantarum induces nitric oxide production in the presence of interferon-\u03b3 in murine macrophages","volume":"48","author":"S-S Kang","year":"2011","journal-title":"Molecular immunology"},{"issue":"6","key":"pone.0281817.ref013","doi-asserted-by":"crossref","first-page":"829","DOI":"10.5851\/kosfa.2014.34.6.829","article-title":"Lysate of probiotic lactobacillus plantarum K8 modulate the mucosal inflammatory system in dextran sulfate sodium-induced colitic rats","volume":"34","author":"Y-S Ahn","year":"2014","journal-title":"Korean journal for food science of animal resources"},{"key":"pone.0281817.ref014","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.cca.2020.08.025","article-title":"Calprotectin in inflammatory bowel disease","volume":"510","author":"F Khaki-Khatibi","year":"2020","journal-title":"Clinica Chimica Acta; International Journal of Clinical Chemistry"},{"issue":"11\u201312","key":"pone.0281817.ref015","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1111\/j.1365-2036.2010.04475.x","article-title":"Pilot study: alterations of intestinal microbiota in obese humans are not associated with colonic inflammation or disturbances of barrier function","volume":"32","author":"J Brignardello","year":"2010","journal-title":"Alimentary pharmacology & therapeutics"},{"issue":"4","key":"pone.0281817.ref016","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1038\/s41385-018-0006-7","article-title":"Oral cholera vaccination promotes homing of IgA+ memory B cells to the large intestine and the respiratory tract","volume":"11","author":"M Van Splunter","year":"2018","journal-title":"Mucosal immunology"},{"issue":"5","key":"pone.0281817.ref017","doi-asserted-by":"crossref","first-page":"4745","DOI":"10.3390\/ijerph110504745","article-title":"Microorganisms with claimed probiotic properties: an overview of recent literature","volume":"11","author":"S. Fijan","year":"2014","journal-title":"International journal of environmental research and public health"},{"issue":"9","key":"pone.0281817.ref018","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1111\/j.1753-4887.2009.00226.x","article-title":"Probiotic microbes: do they need to be alive to be beneficial?","volume":"67","author":"J Kataria","year":"2009","journal-title":"Nutrition reviews"},{"issue":"1","key":"pone.0281817.ref019","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1017\/S0954422410000090","article-title":"The probiotic paradox: live and dead cells are biological response modifiers","volume":"23","author":"CA Adams","year":"2010","journal-title":"Nutrition research reviews"},{"issue":"11","key":"pone.0281817.ref020","doi-asserted-by":"crossref","first-page":"e27961","DOI":"10.1371\/journal.pone.0027961","article-title":"Lysate of probiotic Lactobacillus casei DN-114 001 ameliorates colitis by strengthening the gut barrier function and changing the gut microenvironment","volume":"6","author":"Z Zakostelska","year":"2011","journal-title":"PloS one"},{"issue":"5","key":"pone.0281817.ref021","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1271\/bbb.110919","article-title":"Enhanced immunomodulatory activity and stability in simulated digestive juices of Lactobacillus plantarum L-137 by heat treatment","volume":"76","author":"T Fujiki","year":"2012","journal-title":"Bioscience, biotechnology, and biochemistry"},{"issue":"6\u20137","key":"pone.0281817.ref022","doi-asserted-by":"crossref","first-page":"A486","DOI":"10.1016\/j.autrev.2011.11.023","article-title":"Immunology and the menstrual cycle","volume":"11","author":"S Oertelt-Prigione","year":"2012","journal-title":"Autoimmunity reviews"},{"key":"pone.0281817.ref023","doi-asserted-by":"crossref","DOI":"10.1155\/2014\/159150","article-title":"Sex hormones and immune dimorphism","volume":"2014","author":"A Bhatia","year":"2014","journal-title":"The Scientific World Journal"},{"issue":"6123","key":"pone.0281817.ref024","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1126\/science.1233521","article-title":"Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity","volume":"339","author":"JG Markle","year":"2013","journal-title":"Science"},{"issue":"2","key":"pone.0281817.ref025","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.immuni.2013.08.013","article-title":"Gender bias in autoimmunity is influenced by microbiota","volume":"39","author":"L Yurkovetskiy","year":"2013","journal-title":"Immunity"},{"issue":"4","key":"pone.0281817.ref026","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1080\/19490976.2016.1203502","article-title":"Sex differences and hormonal effects on gut microbiota composition in mice","volume":"7","author":"E Org","year":"2016","journal-title":"Gut microbes"},{"issue":"5","key":"pone.0281817.ref027","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1538\/expanim.57.489","article-title":"Gender difference in the composition of fecal flora in laboratory mice, as detected by denaturing gradient gel electrophoresis (DGGE)","volume":"57","author":"S Fushuku","year":"2008","journal-title":"Experimental animals"},{"issue":"4","key":"pone.0281817.ref028","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1038\/s41385-018-0006-7","article-title":"Oral cholera vaccination promotes homing of IgA+ memory B cells to the large intestine and the respiratory tract","volume":"11","author":"M Van Splunter","year":"2018","journal-title":"Mucosal immunology"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0281817","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T01:52:19Z","timestamp":1677030739000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0281817"}},"subtitle":[],"editor":[{"given":"Brenda A","family":"Wilson","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2023,2,21]]},"references-count":28,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2,21]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0281817","relation":{},"ISSN":["1932-6203"],"issn-type":[{"type":"electronic","value":"1932-6203"}],"subject":[],"published":{"date-parts":[[2023,2,21]]}}}