{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:08:31Z","timestamp":1792789711279,"version":"4.5.0"},"reference-count":43,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Morinaga Milk Industry Co., Ltd.","id":[{"id":"https:\/\/ror.org\/05asq7780","id-type":"ROR","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/04hy75g65","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: This study investigated the effects of bovine lactoferrin (LF) on vaginal microbiota in healthy postmenopausal women. Methods: A randomized, double-blind, placebo-controlled trial was conducted. Healthy Japanese postmenopausal women were administered a placebo or bovine LF (300 mg\/day) for 12 weeks. The primary endpoint was the Nugent score and the secondary endpoints were the Nugent sub-scores. The exploratory outcomes included vaginal immunoglobulin and urinary deoxypyridinoline levels. Results: Eighty participants were randomized (placebo, n = 40; LF, n = 40), of whom 8 were excluded. The remaining 72 participants (placebo group: n = 36; LF group: n = 36) were included in the per-protocol set. Although the Nugent score was lower in the LF group, the difference was not significant. The Gardnerella\/Bacteroides Nugent sub-score was significantly lower in the LF group than in the placebo group. The vaginal immunoglobulin G1 levels were significantly higher in the LF group than in the placebo group. In addition, the urinary deoxypyridinoline levels were significantly lower in the LF group than in the placebo group. Adverse events were comparable between the groups and no adverse drug reactions were observed. Conclusions: Although oral LF supplementation did not significantly affect the primary endpoint (overall Nugent score), a lower Gardnerella\/Bacteroides morphotype score and higher vaginal IgG1 levels were observed. As these findings were derived from secondary and exploratory analyses, respectively, they are considered hypothesis-generating and require confirmation in future studies.<\/jats:p>","DOI":"10.3390\/nu18193193","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T11:35:59Z","timestamp":1790595359000},"page":"3193","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Bovine Lactoferrin on Vaginal Microbiota in Healthy Postmenopausal Women: A Randomized, Double-Blind, Placebo-Controlled Trial"],"prefix":"10.3390","volume":"18","author":[{"given":"Chisane","family":"Kujirai","sequence":"first","affiliation":[{"name":"R&D Division, Food Function Research Institute, Morinaga Milk Industry Co., Ltd., 5-1-83 Higashihara, Zama 252-8583, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2661-1585","authenticated-orcid":false,"given":"Hirotsugu","family":"Oda","sequence":"additional","affiliation":[{"name":"R&D Division, Food Function Research Institute, Morinaga Milk Industry Co., Ltd., 5-1-83 Higashihara, Zama 252-8583, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7670-7366","authenticated-orcid":false,"given":"Miyuki","family":"Tanaka","sequence":"additional","affiliation":[{"name":"R&D Division, Food Function Research Institute, Morinaga Milk Industry Co., Ltd., 5-1-83 Higashihara, Zama 252-8583, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"given":"Yayoi","family":"Sugimori","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Bunkyo Garden Women\u2019s Clinic, 2F, 1-1-7 Koishikawa, Tokyo 112-0002, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"103696","DOI":"10.1016\/j.micpath.2019.103696","article-title":"Crosstalk between Vaginal Microbiome and Female Health: A Review","volume":"136","author":"Gupta","year":"2019","journal-title":"Microb. Pathog."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Amabebe, E., and Anumba, D.O.C. (2018). The Vaginal Microenvironment: The Physiologic Role of Lactobacilli. Front. Med., 5.","DOI":"10.3389\/fmed.2018.00181"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Abou Chacra, L., Fenollar, F., and Diop, K. (2022). Bacterial Vaginosis: What Do We Currently Know?. Front. Cell. Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.672429"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.maturitas.2016.05.015","article-title":"Menopause and the Vaginal Microbiome","volume":"91","author":"Muhleisen","year":"2016","journal-title":"Maturitas"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s11908-022-00794-1","article-title":"Bacterial Vaginosis in Postmenopausal Women","volume":"25","author":"Smith","year":"2023","journal-title":"Curr. Infect. Dis. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1128\/jcm.29.2.297-301.1991","article-title":"Reliability of Diagnosing Bacterial Vaginosis Is Improved by a Standardized Method of Gram Stain Interpretation","volume":"29","author":"Nugent","year":"1991","journal-title":"J. Clin. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.it.2018.01.007","article-title":"Immunology of the Uterine and Vaginal Mucosae","volume":"39","author":"Zhou","year":"2018","journal-title":"Trends Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"eabn9662","DOI":"10.1126\/scitranslmed.abn9662","article-title":"Antibody-Mediated Prevention of Vaginal HIV Transmission Is Dictated by IgG Subclass in Humanized Mice","volume":"14","author":"Brady","year":"2022","journal-title":"Sci. Transl. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1006\/viro.1996.0589","article-title":"Topically Applied Human Recombinant Monoclonal IgG1Antibody and Its Fab and F(Ab\u2032)2Fragments Protect Mice from Vaginal Transmission of HSV-2","volume":"225","author":"Zeitlin","year":"1996","journal-title":"Virology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s00436-008-0971-y","article-title":"Antitrichomonas IgG, IgM, IgA, and IgG Subclass Responses in Human Intravaginal Trichomoniasis","volume":"103","author":"Kaur","year":"2008","journal-title":"Parasitol. Res."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Akiso, M.M., Abook, I., Mureithi, M.W., Kombo, J., Koi, P., Musando, J., Chirchir, R.J., McRaven, M.D., Carias, A.M., and Joseph, S. (2025). Vaginal Microbiome Dysbiosis and Sexually Transmitted Infections Correlate with Concentrations of Immunoglobulin Isotypes in Human Cervicovaginal Mucus: Insights into HIV-1 Transmission. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1627807"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.biochi.2008.05.021","article-title":"Twenty-Five Years of Research on Bovine Lactoferrin Applications","volume":"91","author":"Tomita","year":"2009","journal-title":"Biochimie"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Pino, A., Mazza, T., Matthews, M.-A.H., Castellana, S., Caggia, C., Randazzo, C.L., and Gelbfish, G.A. (2022). Antimicrobial Activity of Bovine Lactoferrin against Gardnerella Species Clinical Isolates. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.1000822"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Artym, J., and Zimecki, M. (2021). Antimicrobial and Prebiotic Activity of Lactoferrin in the Female Reproductive Tract: A Comprehensive Review. Biomedicines, 9.","DOI":"10.3390\/biomedicines9121940"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6341","DOI":"10.1080\/10408398.2021.1900774","article-title":"Oral Fate and Stabilization Technologies of Lactoferrin: A Systematic Review","volume":"62","author":"Wei","year":"2022","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1271\/bbb.121011","article-title":"Intracellular Retention and Subsequent Release of Bovine Milk Lactoferrin Taken Up by Human Enterocyte-Like Cell Lines, Caco-2, C2BBe1 and HT-29","volume":"77","author":"Akiyama","year":"2013","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.semcdb.2021.05.014","article-title":"Interaction between Bone and Immune Cells: Implications for Postmenopausal Osteoporosis","volume":"123","author":"Fischer","year":"2022","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"E1281","DOI":"10.1152\/ajpendo.90938.2008","article-title":"Oral Bovine Lactoferrin Improves Bone Status of Ovariectomized Mice","volume":"296","author":"Blais","year":"2009","journal-title":"Am. J. Physiol.-Endocrinol. Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1002\/jbmr.5650080714","article-title":"Urinary Hydroxypyridinium Crosslinks of Collagen as Markers of Bone Resorption and Estrogen Efficacy in Postmenopausal Osteoporosis","volume":"8","author":"Seibel","year":"1993","journal-title":"J. Bone Miner. Res."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"World Medical Association (2025). World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Participants. JAMA, 333, 71.","DOI":"10.1001\/jama.2024.21972"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"397","DOI":"10.6009\/jjrt.2017_JSRT_73.5.397","article-title":"8. Revised \u201cEthical Guidelines for Medical and Health Research Involving Human Subjects\u201d","volume":"73","author":"Ogasawara","year":"2017","journal-title":"Nippon. Hoshasen Gijutsu Gakkai Zasshi"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.ejogrb.2008.06.003","article-title":"Randomized, Double-Blind, Placebo-Controlled Study of Oral Lactobacilli to Improve the Vaginal Flora of Postmenopausal Women","volume":"141","author":"Petricevic","year":"2008","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1089\/1096620041224166","article-title":"Nucleic Acid-Based Diagnosis of Bacterial Vaginosis and Improved Management Using Probiotic Lactobacilli","volume":"7","author":"Reid","year":"2004","journal-title":"J. Med. Food"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S0928-8244(02)00465-0","article-title":"Oral Use of Lactobacillus Rhamnosus GR-1 and L. Fermentum RC-14 Significantly Alters Vaginal Flora: Randomized, Placebo-Controlled Trial in 64 Healthy Women","volume":"35","author":"Reid","year":"2003","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_25","unstructured":"(2026, August 12). CTCAE and AE Reporting\u2014NCI, Available online: https:\/\/dctd.cancer.gov\/research\/ctep-trials\/for-sites\/adverse-events."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/bmt.2012.244","article-title":"Investigation of the Freely Available Easy-to-Use Software \u2018EZR\u2019 for Medical Statistics","volume":"48","author":"Kanda","year":"2013","journal-title":"Bone Marrow Transpl."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e081123","DOI":"10.1136\/bmj-2024-081123","article-title":"CONSORT 2025 Statement: Updated Guideline for Reporting Randomised Trials","volume":"389","author":"Hopewell","year":"2025","journal-title":"BMJ"},{"key":"ref_28","first-page":"162","article-title":"Influence of Lactoferrin in Preventing Preterm Delivery: A Pilot Study","volume":"5","author":"Cianci","year":"2011","journal-title":"Mol. Med. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"19","DOI":"10.3920\/BM2018.0075","article-title":"Evidence-Based Mixture Containing Lactobacillus Strains and Lactoferrin to Prevent Recurrent Bacterial Vaginosis: A Double Blind, Placebo Controlled, Randomised Clinical Trial","volume":"10","author":"Russo","year":"2019","journal-title":"Benef. Microbes"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1111\/myc.12883","article-title":"Randomised Clinical Trial in Women with Recurrent Vulvovaginal Candidiasis: Efficacy of Probiotics and Lactoferrin as Maintenance Treatment","volume":"62","author":"Russo","year":"2019","journal-title":"Mycoses"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1186\/s12934-020-01464-4","article-title":"Vaginal Microbiota and the Potential of Lactobacillus Derivatives in Maintaining Vaginal Health","volume":"19","author":"Chee","year":"2020","journal-title":"Microb. Cell Fact."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1139\/w05-070","article-title":"Vaginal Microbial Diversity among Postmenopausal Women with and without Hormone Replacement Therapy","volume":"51","author":"Heinemann","year":"2005","journal-title":"Can. J. Microbiol."},{"key":"ref_33","first-page":"CD004143","article-title":"Long-Term Hormone Therapy for Perimenopausal and Postmenopausal Women","volume":"9","author":"Yong","year":"2026","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1017\/S000711452610631X","article-title":"Oral Lactoferrin Reduces Systemic Inflammation, Enhances Anti-Viral Responses and Modulates Immune Cell Profiles: A Randomised Controlled Trial in Healthy, Older Adults","volume":"135","author":"Berthon","year":"2026","journal-title":"Br. J. Nutr."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Oda, H., Kubo, S., Tada, A., Yago, T., Sugita, C., Yoshida, H., Toida, T., Tanaka, M., and Kurokawa, M. (2023). Effects of Bovine Lactoferrin on the Maintenance of Respiratory and Systemic Physical Conditions in Healthy Adults\u2014A Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients, 15.","DOI":"10.3390\/nu15183959"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.2174\/138161209788453202","article-title":"Lactoferrin as a Natural Immune Modulator","volume":"15","author":"Actor","year":"2009","journal-title":"Curr. Pharm. Des."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Takada, K., Melnikov, V.G., Kobayashi, R., Komine-Aizawa, S., Tsuji, N.M., and Hayakawa, S. (2023). Female Reproductive Tract-Organ Axes. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1110001"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1038\/s41586-019-1285-1","article-title":"Migrant Memory B Cells Secrete Luminal Antibody in the Vagina","volume":"571","author":"Oh","year":"2019","journal-title":"Nature"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2653","DOI":"10.1039\/C8FO00303C","article-title":"Lactoferrin Preserves Bone Homeostasis by Regulating the RANKL\/RANK\/OPG Pathway of Osteoimmunology","volume":"9","author":"Fan","year":"2018","journal-title":"Food Funct."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1016\/j.bone.2011.02.002","article-title":"Bovine Lactoferrin Improves Bone Status of Ovariectomized Mice via Immune Function Modulation","volume":"48","author":"Malet","year":"2011","journal-title":"Bone"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1007\/s00011-010-0211-7","article-title":"Inflammatory Responses Improve with Milk Ribonuclease-Enriched Lactoferrin Supplementation in Postmenopausal Women","volume":"59","author":"Bharadwaj","year":"2010","journal-title":"Inflamm. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1007\/s00198-009-0839-8","article-title":"Milk Ribonuclease-Enriched Lactoferrin Induces Positive Effects on Bone Turnover Markers in Postmenopausal Women","volume":"20","author":"Bharadwaj","year":"2009","journal-title":"Osteoporos. Int."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2048","DOI":"10.1093\/infdis\/jiaa675","article-title":"Bacterial Communities Associated with Abnormal Nugent Score in Postmenopausal Versus Premenopausal Women","volume":"223","author":"Mitchell","year":"2021","journal-title":"J. Infect. Dis."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/19\/3193\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:16:26Z","timestamp":1790741786000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/19\/3193"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,27]]},"references-count":43,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["nu18193193"],"URL":"https:\/\/doi.org\/10.3390\/nu18193193","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,27]]}}}