Oral Administration of Lacticaseibacillus paracasei CCFM 1433 Boosts Host Immunity to Prevent Candida albicans Infections

Authors

Xinya ZHANG, School of Food Science and Technology , Jiangnan University , Wuxi 214122 , China
Qiuxiang ZHANG, School of Food Science and Technology , Jiangnan University , Wuxi 214122 , ChinaFollow
Xin TANG, School of Food Science and Technology , Jiangnan University , Wuxi 214122 , China
Bingyong MAO, School of Food Science and Technology , Jiangnan University , Wuxi 214122 , China
Jianxin ZHAO, School of Food Science and Technology , Jiangnan University , Wuxi 214122 , China
Shumao CUI, School of Food Science and Technology , Jiangnan University , Wuxi 214122 , China

Corresponding Author(s)

张秋香（1979—），女，博士，教授，博士研究生导师，主要从事益生菌理论与技术、特殊生境益生菌功能发掘、口腔微生态与健康研究。E-mail：zhangqx@jiangnan.edu.cn

Abstract

[Objective ] This study aims to explore the role of Lactobacillus in enhancing host immunocompetence and preventing vaginal infections with Candida albicans.[Method ] A human vaginal epithelial cell (VK2/E6E7 cell) model was employed to screen the most potent strain among ten vaginal Lactobacillus isolates in inducing the antimicrobial peptide LL- 37.A mouse model of vaginal infection with Candida albicans was established.The effects of oral administration of the selected Lactobacillus strain on vaginal mucosal immunity,systemic inflammatory balance,and vaginal microbiota homeostasis were systematically evaluated using hematoxylin-eosin (HE) staining,ELISA,qPCR,and 16S rRNA sequencing.[Result ] Both t he cell lysate and fermentation supernatant of Lacticaseibacillus paracasei CCFM 1433 upregulated antimicrobial peptide LL-37 secretion in VK2/E6E7 cells by 22.5% and 12.3%,respectively,compared with the control group,exhibiting superior activity over those of other strains.Live Lacticaseibacillus paracasei CCFM 1433 increased the level of cathelicidin- related anti microbial peptide (CRAMP ) in the vaginal tissue to 1.82 times that of the model group,increased the level of secretory immunoglobulin A (sIgA ) by 52.9%,and the level of immunoglobulin G (IgG) in the serum by 16.9% compared with the model group.It also increased the level of IL- 10 in the spleen by 23.9%,while reducing the TNF- α level by 20.3%.In addition,both live Lacticaseibacillus paracasei CCFM 1433 and its postbiotics inhibited the TLR 4/MyD 88 signaling pathway,preventing overactivation of inflammatory pathways.The 16S rRNA sequencing results indicated that the live bacteria of this strain effectively maintained the vaginal homeostasis of Lactobacillus communities and its intervention effect was closely associated with a significant enrichment of functional genes in the signaling molecules and interaction pathway in the mouse vaginal microbiome.[Conclusion ] Lacticaseibacillus paracasei CCFM 1433 exerts an anti-infection effect and effectiv ely prevents Candida albicans infections by directly activating host mucosal immunity,modulating inflammatory responses,and restoring the Lactobacillus -dominant vaginal microbiota.These findings provide theoretical support for the application of probiotics in preventing vaginal infections.

Publication Date

8-15-2025

First Page

162

Last Page

172

DOI

10.12441/spyswjs.20250315001

Recommended Citation

ZHANG, Xinya; ZHANG, Qiuxiang; TANG, Xin; MAO, Bingyong; ZHAO, Jianxin; and CUI, Shumao (2025) "Oral Administration of Lacticaseibacillus paracasei CCFM 1433 Boosts Host Immunity to Prevent Candida albicans Infections," Journal of Food Science and Biotechnology: Vol. 44: Iss. 8, Article 17.
DOI: 10.12441/spyswjs.20250315001
Available at: https://spsw.spyswjs.cnjournals.com/journal/vol44/iss8/17

References

［1］ 廖秦平.女性阴道微生态及阴道微生态评价 ［J］.实用妇产科杂志，2010，26（2）：81-83.LIAO Q P.Female vaginal microecology and evaluation of vaginal microecology ［J］.Journal of Practical Obstetrics and Gynecology，2010，26（2）：81-83.（in Chinese）
［2］ QIN L，SUN T Y，LI X，et al.Population-level analyses identify host and environmental variables influencing the vaginal microbiome ［J］.Signal Transduction and Targeted Therapy，2025，10：64.
［3］ WITKIN S S，LINHARES I M.Why do lactobacilli dominate the human vaginal microbiota ？ ［J］.BJOG，2017，124（4）：606-611.
［4］ LEBEER S，AHANNACH S，GEHRMANN T，et al.A citizen-science-enabled catalogue of the vaginal microbiome and associated factors ［J］.Nature Microbiology，2023，8（11）：2183 -2195.
［5］ CHEE W J Y，CHEW S Y，Than L T L.Vaginal microbiota and the potential of Lactobacillus derivatives in maintaining vaginal health ［J］.Microbial Cell Factories，2020，19：203.
［6］ SELLE K，KLAENHAMMER T R.Genomic and phenotypic evidence for probiotic influences of Lactobacillus gasseri on human health ［J］.FEMS Microbiology Reviews，2013，37（6）：915-935.
［7］ O’HANLON D E，MOENCH T R，CONE R A.Vaginal pH and microbicidal lactic acid when lactobacilli dominate the microbiota ［J］.PLoS One，2013，8（11）：e80074.
［8］ MIKO E，BARAKONYI A.The role of hydrogen-peroxide （H2O2） produced by vaginal microbiota in female reproductive health ［J］.Antioxidants，2023，12（5）：1055.
［9］ STOYANCHEVA G，MARZOTTO M，DELLAGLIO F，et al.Bacteriocin production and gene sequencing analysis from vaginal Lactobacillus strains［J］.Archives of Microbiology，2014，196（9）：645-653.
［10］ 纪凌云，吴晶，周旸，等.阴道微生物组与 HPV感染和宫颈病变的相关性研究进展 ［J］.微生物与感染，2023，18（4）：251-256.JI L Y，WU J，ZHOU Y，et al.Research progress on vaginal microbiome and its relationship with human papillomavirus infection and cervical disease ［J］.Journal of Microbes and Infections，2023，18（4）：251-256.（in Chinese ）
［11］ 何一宁，熊海燕，郑英杰.阴道乳杆菌与早产关系的研究进展［J］.中华流行病学杂志，2017，38（3）：406-410.HE Y N，XIONG H Y，ZHENG Y J.Progress in research of relationship between vaginal Lactobacillus and preterm delivery［J］.Chinese Journal of Epidemiology，2017，38（3）：406-410.（in Chinese ）
［12］ KAUSHIC C.The role of the local microenvironment in regulating susceptibility and immune responses to sexually transmitted viruses in the female genital tract ［J］.Journal of Reproductive Immunology，2009，83（1/2）：168-172.
［13］ KESHRI A K，RAWAT S S，CHAUDHARY A，et al.LL-37，the master antimicrobial peptide，its multifaceted role from combating infections to cancer immunity ［J］.International Journal of Antimicrobial Agents，2025，65（1）：107398.
［14］ KHURSHID Z，NASEEM M，ASIRI F Y I，et al.Significance and diagnostic role of antimicrobial cathelicidins （LL-37） peptides in oral health ［J］.Biomolecules，2017，7（4）：80.
［15］ VANDAMME D，LANDUYT B，LUYTEN W，et al.A comprehensive summary of LL- 37，the factotum human cathelicidin peptide ［J］.Cellular Immunology，2012，280（1）：22-35.
［16］ 杨利林，罗颂平，朱玲.生殖道局部 sIgA的作用及研究进展［J］.中国中医药现代远程教育，2014，12（2）：160-162.YANG L L，LUO S P，ZHU L.The role and research progress of sIgA in local reproductive tract ［J］.Chinese Medicine Modern Distance Education of China，2014，12（2）：160-162.（in Chinese ）
［17］ HEMATIANLARKI M，NIMMERJAHN F.Immunomodulatory and anti-inflammatory properties of immunoglobulin G antibodies ［J］.Immunological Reviews，2024，328（1）：372-386.
［18］ LIU Q，LIU Q Y，MENG H W，et al.Staphylococcus epidermidis contributes to healthy maturation of the nasal microbiome by stimulating antimicrobial peptide production［J］.Cell Host & Microbe，2020，27（1）：68-78.
［19］ SI W，LIANG H，BUGNO J，et al.Lactobacillus rhamnosus GG induces cGAS/STING-dependent type I interferon and improves response to immune checkpoint blockade［J］.Gut，2022，71（3）：521-533.
［20］ 林 如 梦，黄 小 艳，崔 树 茂，等.副 干 酪 乳 酪 杆 菌CCFM 1317激活 Keap 1/Nrf2通路缓解小鼠阴道加德纳菌感染［J］.食品与发酵工业，2025，51（3）：21-27.LIN R M，HUANG X Y，CUI S M，et al.Lacticaseibacillus paracasei CCFM 1317 alleviates Gardnerella vaginalis infection in mice by activating expression of Keap 1/Nrf2 pathway ［J］.Food and Fermentation Industries，2025，51（3）：21-27.（in Chinese ）［21］ HUANG X Y，LIN R M，MAO B Y，et al.Lactobacillus crispatus CCFM 1339 inhibits vaginal epithelial barrier injury induced by Gardnerella vaginalis in mice ［J］.Biomolecules，2024，14（2）：240.
［22］ ZHANG J Y，PENG J W，LI D M，et al.Divergent EGFR/MAPK-mediated immune responses to clinical Candida pathogens in vulvovaginal candidiasis ［J］.Frontiers in Immunology，2022，13：894069.
［23］ LI S，HERRERA G G，TAM K K，et al.Estrogen action in the epithelial cells of the mouse vagina regulates neutrophil infiltration and vaginal tissue integrity ［J］.Scientific Reports，2018，8：11247.
［24］ PEKMEZOVIC M，HOVHANNISYAN H，GRESNIGT M S，et al.Candida pathogens induce protective mitochondria-associated type I interferon signalling and a damage-driven response in vaginal epithelial cells ［J］.Nature Microbiology，2021，6（5）：643-657.
［25］ PIRCHER J，CZERMAK T，EHRLICH A，et al.Cathelicidins prime platelets to mediate arterial thrombosis and tissue inflammation ［J］.Nature Communication s，2018，9：1523.
［26］ ZHANG C，DING Y，LIU Y F，et al.The role of TLR 4-mediated MyD 88/TRAF 6/NF- κB signaling and pIgR intestinal expression in chicks during Salmonella enteritidis infection ［J］.Veterinary Immunology and Immunopathology，2023，258：110563.
［27］ KAUSHIC C，FRAUENDORF E，WIRA C R.Polymeric immunoglobulin a receptor in the rodent female reproductive tract：influence of estradiol in the vagina and differential expression of messenger ribonucleic acid during estrous cycle ［J］.Biology of Reproduction，1997，57（5）：958-966.
［28］ KALIA N，SINGH J，KAUR M.Immunopathology of recurrent vulvovaginal infections：new aspects and research directions［J］.Frontiers in Immunology，2019，10：2034.
［29］ TSAI W C，LIU F L，HUANG M H，et al.Enhancing immunity and modulating vaginal microflora against candidal vaginitis through nanoemulsion supplemented with Porphyra oligosaccharide as an intravaginal vaccine adjuvant［J］.International Journal of Nanomedicine，2023，18：6333 -6346.
［30］ WEINDL G，NAGLIK J R，KAESLER S，et al.Human epithelial cells establish direct antifungal defense through TLR 4-mediated signaling ［J］.The Journal of Clinical Investigation，2007，117（12）：3664 -3672.
［31］ WU H，LI C，WANG Y M，et al.Transcriptomics reveals effect of Pulsatilla decoction butanol extract in alleviating vulvovaginal candidiasis by inhibiting neutrophil chemotaxis and activation via TLR 4 signaling ［J］.Pharmaceuticals，2024，17（5）：594.