Exploring New Treatments for Bacterial Vaginosis: Evaluating the Synergistic Effects of Prebiotics and Lactic Acid on Lactobacillus Crispatus growth
DOI:
https://doi.org/10.58445/rars.3215Keywords:
Bacterial vaginosis, biofilms, Lactobacillus crispatus, prebiotics, probiotics, postbiotics, glycogen, inulin, D-mannose, lactic acidAbstract
Background: Bacterial vaginosis (BV) is a common vaginal condition caused by an imbalance in the microbiome. Lactobacillus crispatus plays a key role in vaginal health by producing lactic acid, which lowers pH and inhibits growth of bacteria causing BV. Prebiotic and postbiotic compounds such as D-mannose, glycogen, inulin and lactic acid might help restore a healthy vaginal microenvironment by stimulating growth of L. crispatus.
Methods: Concentrations of D-mannose, glycogen, inulin, and lactic acid for enhancing L. crispatus were screened. Growth curves of L. crispatus in the presence and absence of these compounds (1–10 mg/ml, LMRS media) were obtained from 16-hour incubations, and biofilm assays were performed on select concentrations.
Results: Specific prebiotic and postbiotic enhancers can significantly promote the growth of L. crispatus in liquid media when added in the concentration range of 1-6 mg/ml. Inulin (I) was the most efficient enhancer (31-56% relative enhancement) of the three prebiotics. The combination of D-mannose (M) and glycogen (G) had the strongest relative enhancement (152%). Adding D-lactic acid (DLA) in a triple combination increased growth rates across all combinations, with G+I+DLA mix yielding the highest enhancement (162%). Biofilms data showed dramatic enhancements for the following combinations: 208% for M+G+DLA, 177% for G+I+DLA, and 144% for M+I+DLA.
Conclusions: This preliminary study highlights the potential of enhancer supplementation to stimulate regrowth of L. crispatus, which could be the foundation of a viable strategy in the treatment of recurrent BV.
References
Cohen CR, Lingappa JR, Baeten JM, et al. Bacterial Vaginosis Associated with Increased Risk of Female-to-Male HIV-1 Transmission: A Prospective Cohort Analysis among African Couples. PLOS Medicine. 2012;9(6):e1001251. doi:10.1371/journal.pmed.1001251
De Seta F, Campisciano G, Zanotta N, Ricci G, Comar M. The Vaginal Community State Types Microbiome-Immune Network as Key Factor for Bacterial Vaginosis and Aerobic Vaginitis. Front Microbiol. 2019;10:2451. doi:10.3389/fmicb.2019.02451
Chee WJY, Chew SY, Than LTL. Vaginal microbiota and the potential of Lactobacillus derivatives in maintaining vaginal health. Microb Cell Fact. 2020;19(1):203. doi:10.1186/s12934-020-01464-4
Breshears LM, Edwards VL, Ravel J, Peterson ML. Lactobacillus crispatus inhibits growth of Gardnerella vaginalis and Neisseria gonorrhoeae on a porcine vaginal mucosa model. BMC Microbiology. 2015;15(1):276. doi:10.1186/s12866-015-0608-0
France M, Alizadeh M, Brown S, Ma B, Ravel J. Towards a deeper understanding of the vaginal microbiota. Nature Microbiology. 2022;7(3):367-378. doi:10.1038/s41564-022-01083-2
Tachedjian G, Aldunate M, Bradshaw CS, Cone RA. The role of lactic acid production by probiotic Lactobacillus species in vaginal health. Research in Microbiology. 2017;168(9):782-792. doi:10.1016/j.resmic.2017.04.001
Mitchell C, Fredricks D, Agnew K, Hitti J. Hydrogen-peroxide producing lactobacilli are associated with lower levels of vaginal IL1β, independent of bacterial vaginosis. Sex Transm Dis. 2015;42(7):358-363. doi:10.1097/OLQ.0000000000000298
Vodstrcil LA, Muzny CA, Plummer EL, Sobel JD, Bradshaw CS. Bacterial vaginosis: drivers of recurrence and challenges and opportunities in partner treatment. BMC Medicine. 2021;19(1):194. doi:10.1186/s12916-021-02077-3
Bradshaw CS, Morton AN, Hocking J, et al. High Recurrence Rates of Bacterial Vaginosis over the Course of 12 Months after Oral Metronidazole Therapy and Factors Associated with Recurrence. The Journal of Infectious Diseases. 2006;193(11):1478-1486. doi:10.1086/503780
Ji J, Jin W, Liu S, Jiao Z, Li X. Probiotics, prebiotics, and postbiotics in health and disease. MedComm (2020). 2023;4(6):e420. doi:10.1002/mco2.420
Cohen CR, Wierzbicki MR, French AL, et al. Randomized Trial of Lactin-V to Prevent Recurrence of Bacterial Vaginosis. New England Journal of Medicine. 2020;382(20):1906-1915. doi:10.1056/NEJMoa1915254
Shen X, Xu L, Zhang Z, et al. Postbiotic gel relieves clinical symptoms of bacterial vaginitis by regulating the vaginal microbiota. Front Cell Infect Microbiol. 2023;13. doi:10.3389/fcimb.2023.1114364
Wagenlehner F, Lorenz H, Ewald O, Gerke P. Why d-Mannose May Be as Efficient as Antibiotics in the Treatment of Acute Uncomplicated Lower Urinary Tract Infections—Preliminary Considerations and Conclusions from a Non-Interventional Study. Antibiotics (Basel). 2022;11(3):314. doi:10.3390/antibiotics11030314
Caretto M, Giannini A, Russo E, Simoncini T. Preventing urinary tract infections after menopause without antibiotics. Maturitas. 2017;99:43-46. doi:10.1016/j.maturitas.2017.02.004
Hertzberger R, May A, Kramer G, van Vondelen I, Molenaar D, Kort R. Genetic Elements Orchestrating Lactobacillus crispatus Glycogen Metabolism in the Vagina. Int J Mol Sci. 2022;23(10):5590. doi:10.3390/ijms23105590
Navarro S, Abla H, Delgado B, Colmer-Hamood JA, Ventolini G, Hamood AN. Glycogen availability and pH variation in a medium simulating vaginal fluid influence the growth of vaginal Lactobacillus species and Gardnerella vaginalis. BMC Microbiology. 2023;23(1):186. doi:10.1186/s12866-023-02916-8
Jenkins DJ, Woolston BM, Hood-Pishchany MI, et al. Bacterial amylases enable glycogen degradation by the vaginal microbiome. Nat Microbiol. 2023;8(9):1641-1652. doi:10.1038/s41564-023-01447-2
Tachedjian G, Aldunate M, Bradshaw CS, Cone RA. The role of lactic acid production by probiotic Lactobacillus species in vaginal health. Research in Microbiology. 2017;168(9):782-792. doi:10.1016/j.resmic.2017.04.001
Jolliff JS, Mahan DC. Effect of Dietary Inulin and Phytase on Mineral Digestibility and Tissue Retention in Weanling and Growing Swine1,2. J Anim Sci. 2012;90(9):3012-3022. doi:10.2527/jas.2011-4424
Wu XZ, Wen ZG, Hua JL. Effects of dietary inclusion of Lactobacillus and inulin on growth performance, gut microbiota, nutrient utilization, and immune parameters in broilers. Poultry Science. 2019;98(10):4656-4663. doi:10.3382/ps/pez166
O’Hanlon DE, Gajer P, Brotman RM, Ravel J. Asymptomatic Bacterial Vaginosis Is Associated With Depletion of Mature Superficial Cells Shed From the Vaginal Epithelium. Front Cell Infect Microbiol. 2020;10:106. doi:10.3389/fcimb.2020.00106
Delgado-Diaz DJ, Jesaveluk B, Hayward JA, et al. Lactic acid from vaginal microbiota enhances cervicovaginal epithelial barrier integrity by promoting tight junction protein expression. Microbiome. 2022;10(1):141. doi:10.1186/s40168-022-01337-5
Giordani B, Naldi M, Croatti V, et al. Exopolysaccharides from vaginal lactobacilli modulate microbial biofilms. Microbial Cell Factories. 2023;22(1):45. doi:10.1186/s12934-023-02053-x
Downloads
Posted
Categories
License
Copyright (c) 2025 Lehan Gu, Elizabeth Krider, Manjula Gunawardana
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.