{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T22:39:19Z","timestamp":1790894359313,"version":"4.1.0"},"reference-count":41,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T00:00:00Z","timestamp":1638835200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2017R1A5A2014768"],"award-info":[{"award-number":["NRF-2017R1A5A2014768"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003052","name":"Ministry of Trade, Industry and Energy","doi-asserted-by":"publisher","award":["MOTIE, RCC18005"],"award-info":[{"award-number":["MOTIE, RCC18005"]}],"id":[{"id":"10.13039\/501100003052","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Korea Industrial Complex Corp","award":["KICOX"],"award-info":[{"award-number":["KICOX"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Foods"],"abstract":"<jats:p>We previously reported that the immunostimulatory activity of heat-killed Latilactobacillus sakei K040706 in macrophages and cyclophosphamide (CTX)-treated mice. However, identification of heat-killed L. sakei K040706 (heat-killed LS06) using a validated method is not yet reported. Further, the underlying molecular mechanisms for its immunostimulatory effects in CTX-induced immunosuppressed mice remain unknown. In this study, we developed strain-specific genetic markers to detect heat-killed L. sakei LS06. The lower detection limit of the validated primer set was 2.1 \u00d7 105 colony forming units (CFU)\/mL for the heat-killed LS06 assay. Moreover, oral administration of heat-killed LS06 (108 or 109 CFU\/day, p.o.) effectively improved the body loss, thymus index, natural killer cell activity, granzyme B production, and T and B cell proliferation in CTX-treated mice. In addition, heat-killed LS06 enhanced CTX-reduced immune-related cytokine (interferon-\u03b3, interleukin (IL)-2, and IL-12) production and mRNA expression. Heat-killed LS06 also recovered CTX-altered microbiota composition, including the phylum levels of Bacteroidetes, Firmicutes, and Proteobacteria and the family levels of Muribaculaceae, Prevotellaceae, Tannerellaceae, Christensenellaceae, Gracilibacteraceae, and Hungateiclostridiaceae. In conclusion, since heat-killed L. sakei K040706 ameliorated CTX-induced immunosuppression and modulated gut microbiota composition, they have the potential to be used in functional foods for immune regulation.<\/jats:p>","DOI":"10.3390\/foods10123034","type":"journal-article","created":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T02:48:13Z","timestamp":1638845293000},"page":"3034","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Strain-Specific Identification and In Vivo Immunomodulatory Activity of Heat-Killed Latilactobacillus sakei K040706"],"prefix":"10.3390","volume":"10","author":[{"given":"Kyung-Sook","family":"Chung","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9436-6369","authenticated-orcid":false,"given":"Jae Woong","family":"Choi","sequence":"additional","affiliation":[{"name":"Korea Food Research Institute, 245, Nongsaengmyeong-ro, Iseo-myeon, Wanju-gun 55365, Jeollabuk-do, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Sun","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seo-Yeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul 02447, Korea"},{"name":"Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee-Soo","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul 02447, Korea"},{"name":"Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su-Yeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul 02447, Korea"},{"name":"Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwang-Young","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo-Yeon","family":"Kang","sequence":"additional","affiliation":[{"name":"NOVAREX Co., Ltd., 94, Gangni 1-gil, Ochang-eup, Cheongwon-gu, Cheongju-si 363-885, Chungcheongbuk-do, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0496-8046","authenticated-orcid":false,"given":"Chang-Won","family":"Cho","sequence":"additional","affiliation":[{"name":"Korea Food Research Institute, 245, Nongsaengmyeong-ro, Iseo-myeon, Wanju-gun 55365, Jeollabuk-do, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee-Do","family":"Hong","sequence":"additional","affiliation":[{"name":"Korea Food Research Institute, 245, Nongsaengmyeong-ro, Iseo-myeon, Wanju-gun 55365, Jeollabuk-do, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Kyoung","family":"Rhee","sequence":"additional","affiliation":[{"name":"Korea Food Research Institute, 245, Nongsaengmyeong-ro, Iseo-myeon, Wanju-gun 55365, Jeollabuk-do, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3141-3727","authenticated-orcid":false,"given":"Kyung-Tae","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul 02447, Korea"},{"name":"Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"253","DOI":"10.3923\/ijp.2015.253.290","article-title":"Effect of Immunomodulation and immunomodulatory agents on health with some bioactive principles, modes of action and potent biomedical applications","volume":"11","author":"Dhama","year":"2015","journal-title":"Int. J. Pharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1097\/00054725-199911000-00009","article-title":"Th1\/Th2 cells","volume":"5","author":"Romagnani","year":"1999","journal-title":"Inflamm. Bowel. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/nri.2017.118","article-title":"TH2 cell development and function","volume":"18","author":"Walker","year":"2018","journal-title":"Nat. Rev. Immunol."},{"key":"ref_4","first-page":"e24","article-title":"Immunomodulatory drugs: Oral and systemic adverse effects","volume":"19","author":"Mattila","year":"2014","journal-title":"Med. Oral Patol. Oral Cir. Bucal"},{"key":"ref_5","first-page":"223","article-title":"Th1\/Th2 balance: The hypothesis, its limitations, and implications for health and disease","volume":"8","author":"Kidd","year":"2003","journal-title":"Altern. Med. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"655","DOI":"10.3389\/fpls.2015.00655","article-title":"Plant-derived immunomodulators: An insight on their preclinical evaluation and clinical trials","volume":"6","author":"Jantan","year":"2015","journal-title":"Front. Plant. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1099\/00207713-44-4-846","article-title":"Taxonomic note: A place for DNA-DNA reassociation and 16S rRNA sequence analysis in the present species definition in bacteriology","volume":"44","author":"Stackebrandt","year":"1994","journal-title":"Int. J. Syst. Evol. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1128\/mr.60.2.407-438.1996","article-title":"Polyphasic taxonomy, a consensus approach to bacterial systematics","volume":"60","author":"Vandamme","year":"1996","journal-title":"Microbiol. Rev."},{"key":"ref_9","first-page":"39","article-title":"Methods for analysis of the intestinal microflora","volume":"1","year":"2000","journal-title":"Curr. Issues Intest. Microbiol."},{"key":"ref_10","unstructured":"Choi, J.W., Rhee, Y.K., Hong, H.D., Cho, C.W., Lee, Y.C., Lim, T.G., and Kim, J.S. (2020). A primer set for Specifically Detecting Lactobacillus sakei and uses thereof. (No. 1021454080000), K.R. Patent."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.intimp.2015.05.037","article-title":"Lactobacillus sakei K040706 evokes immunostimulatory effects on macrophages through TLR 2-mediated activation","volume":"28","author":"Jung","year":"2015","journal-title":"Int. Immunopharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.jff.2016.12.045","article-title":"Anti-colitis effect of Lactobacillus sakei K040706 via suppression of inflammatory responses in the dextran sulfate sodium-induced colitis mice model","volume":"29","author":"Seo","year":"2017","journal-title":"J. Funct. Foods"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Kim, S.Y., Shin, J.S., Chung, K.S., Han, H.S., Lee, H.H., Lee, J.H., Kim, S.Y., Ji, Y.W., Ha, Y., and Kang, J. (2020). Immunostimulatory effects of live Lactobacillus sakei K040706 on the CYP-induced immunosuppression mouse model. Nutrients, 12.","DOI":"10.3390\/nu12113573"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1099\/ijsem.0.001755","article-title":"Introducing EzBioCloud: A taxonomically united database of 16S rRNA gene sequences and whole-genome assemblies","volume":"67","author":"Yoon","year":"2017","journal-title":"Int. J. Syst. Evol. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1002\/ptr.5960","article-title":"Immunostimulatory effects of cordycepin-enriched WIB-801CE from Cordyceps militaris in splenocytes and cyclophosphamide-induced immunosuppressed mice","volume":"32","author":"Shin","year":"2018","journal-title":"Phytother. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1016\/j.ijbiomac.2019.10.062","article-title":"Immunostimulatory effects of polysaccharides isolated from young barley leaves (Hordeum vulgare L.) with dual activation of Th1 and Th2 in splenic T cells and cyclophosphamide-induced immunosuppressed mice","volume":"147","author":"Han","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/s12275-018-8014-6","article-title":"UBCG: Up-to-date bacterial core gene set and pipeline for phylogenomic tree reconstruction","volume":"56","author":"Na","year":"2018","journal-title":"J. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.cell.2014.03.011","article-title":"Role of the microbiota in immunity and inflammation","volume":"157","author":"Belkaid","year":"2014","journal-title":"Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.bmc.2003.10.006","article-title":"Effect of abietane diterpenes from Plectranthus grandidentatus on T- and B-lymphocyte proliferation","volume":"12","author":"Cerqueira","year":"2004","journal-title":"Bioorg. Med. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1136\/pgmj.2003.008664","article-title":"Probiotics and human health: A clinical perspective","volume":"80","author":"Gill","year":"2004","journal-title":"Postgrad. Med. J."},{"key":"ref_21","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":"Kataria","year":"2009","journal-title":"Nutr. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.4315\/0362-028X-71.8.1734","article-title":"Safety aspects and implications of regulation of probiotic bacteria in food and food supplements","volume":"71","author":"Wassenaar","year":"2008","journal-title":"J. Food Prot."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e795","DOI":"10.1542\/peds.2006-2930","article-title":"An experimental study and a randomized, double-blind, placebo-controlled clinical trial to evaluate the antisecretory activity of Lactobacillus acidophilus strain LB against nonrotavirus diarrhea","volume":"120","author":"Servin","year":"2007","journal-title":"Pediatrics"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1203\/PDR.0b013e3181aabd4f","article-title":"Live and heat-killed Lactobacillus rhamnosus GG: Effects on proinflammatory and anti-inflammatory cytokines\/chemokines in gastrostomy-fed infant rats","volume":"66","author":"Li","year":"2009","journal-title":"Pediatr. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"48","DOI":"10.3168\/jds.S0022-0302(98)75549-3","article-title":"The effect of oral feeding of Lactobacillus casei strain Shirota on immunoglobulin E production in mice","volume":"81","author":"Matsuzaki","year":"1998","journal-title":"J. Dairy Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"M260","DOI":"10.1111\/j.1750-3841.2011.02161.x","article-title":"Heat-killed lactic acid bacteria enhance immunomodulatory potential by skewing the immune response toward Th1 polarization","volume":"76","author":"Ou","year":"2011","journal-title":"J. Food Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"887","DOI":"10.3920\/BM2015.0009","article-title":"Strategies to develop strain-specific PCR based assays for probiotics","volume":"6","author":"Treven","year":"2015","journal-title":"Benef. Microbes"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"595902","DOI":"10.3389\/fmicb.2020.595902","article-title":"Molecular pap smear: Validation of HPV genotype and host methylation profiles of ADCY8, CDH8, and ZNF582 as a predictor of cervical cytopathology","volume":"11","author":"Xia","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"103485","DOI":"10.1016\/j.fm.2020.103485","article-title":"Novel real-time PCR assay for Lactobacillus casei group species using comparative genomics","volume":"90","author":"Kim","year":"2020","journal-title":"Food Microbiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"111395","DOI":"10.1016\/j.lwt.2021.111395","article-title":"Rapid strain-specific identification of two Lactobacillus rhamnosus strains using PCR based on gene family analysis","volume":"146","author":"Chenchen","year":"2021","journal-title":"LWT"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.thorsurg.2018.12.001","article-title":"The role of the thymus in the immune response","volume":"29","author":"Thapa","year":"2019","journal-title":"Thorac. Surg. Clin."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"10397","DOI":"10.1039\/D0FO02272A","article-title":"Modulation of gut homeostasis by exopolysaccharides from Aspergillus cristatus (MK346334), a strain of fungus isolated from Fuzhuan brick tea, contributes to immunomodulatory activity in cyclophosphamide-treated mice","volume":"11","author":"Xie","year":"2020","journal-title":"Food Funct."},{"key":"ref_33","first-page":"383","article-title":"Cyclophosphamide-induced eosinophilia in the rat: Concomitant changes in T-cell subsets, B cells and large granular lymphocytes within lymphoid tissues","volume":"60","author":"Thomson","year":"1987","journal-title":"Immunology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/0300-483X(91)90196-8","article-title":"Roles of dosage, pharmacokinetics, and cellular sensitivity to damage in the selective toxicity of cyclophosphamide towards B and T cells in development","volume":"66","author":"Misra","year":"1991","journal-title":"Toxicology"},{"key":"ref_35","first-page":"37","article-title":"Immunomodulatory effects of probiotics in the intestinal tract","volume":"10","author":"Delcenserie","year":"2008","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"9097","DOI":"10.1126\/science.aay9097","article-title":"Multi-omics analyses of radiation survivors identify radioprotective microbes and metabolites","volume":"370","author":"Guo","year":"2020","journal-title":"Science"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e1258506","DOI":"10.1080\/2162402X.2016.1258506","article-title":"The influence of gut-decontamination prophylactic antibiotics on acute graft-versus-host disease and survival following allogeneic hematopoietic stem cell transplantation","volume":"6","author":"Routy","year":"2017","journal-title":"Oncoimmunology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"104057","DOI":"10.1016\/j.jff.2020.104057","article-title":"Effects of polysaccharides from bee collected pollen of Chinese wolfberry on immune response and gut microbiota composition in cyclophosphamide-treated mice","volume":"72","author":"Zhao","year":"2020","journal-title":"J. Funct. Foods"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3331","DOI":"10.3389\/fmicb.2018.03331","article-title":"Fecal microbiota of toxigenic Clostridioides difficile-associated diarrhea","volume":"9","author":"Quijada","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"701566","DOI":"10.3389\/fmicb.2021.701566","article-title":"Effects of Lycium barbarum polysaccharides on immunity and the gut microbiota in cyclophosphamide-induced immunosuppressed mice","volume":"12","author":"Wang","year":"2021","journal-title":"Front. Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"fix153","DOI":"10.1093\/femsec\/fix153","article-title":"Identification of universal gut microbial biomarkers of common human intestinal diseases by meta-analysis","volume":"93","author":"Mancabelli","year":"2017","journal-title":"FEMS Microbiol. Ecol."}],"container-title":["Foods"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2304-8158\/10\/12\/3034\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:42:11Z","timestamp":1760168531000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2304-8158\/10\/12\/3034"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,7]]},"references-count":41,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["foods10123034"],"URL":"https:\/\/doi.org\/10.3390\/foods10123034","relation":{},"ISSN":["2304-8158"],"issn-type":[{"value":"2304-8158","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,7]]}}}