Protective Mechanisms of Vaginal Lactobacilli against Sexually Transmitted Viral Infections
Abstract
:1. Vaginal Microbiota in Health and Disease
1.1. The Microbiome of the Female Reproductive Tract
1.2. Community State Types (CSTs)
1.3. Vaginal Eubiosis and Dysbiosis
2. Vaginal Lactobacilli: Physiological Roles and Molecular Mechanisms against Pathogens
2.1. Mechanisms Relying on Metabolites Produced by Lactobacilli
2.2. Mechanisms Relying on Lactobacilli Interactions
3. Sexually Transmitted Infections (STIs) and Viral STIs
3.1. STIs Public Health Issues
3.2. STIs Transmission
3.3. Viral STIs Epidemiology and Public Health Prevention Strategies
4. Lactobacilli and Viral STIs
4.1. HPV
4.2. HIV
4.3. HSV
4.4. Other Viruses
5. Towards Lactobacilli as Biotherapeutics for Viral STIs
5.1. Drug Resistance in Viral Treatment: A Growing Issue
5.2. Lactobacilli as a Promising Alternative for Treating Viral STIs
6. Conclusions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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Virus | Lactobacillus Species/Strain | Antiviral Effect | Metabolites and/or Molecular Mechanism | Targeted Organ/Cell Type/Model Cell Line | Ref |
---|---|---|---|---|---|
HPV | n.d. (combination of species) | reduced virus colonization | cytokine network | cervix, vagina, urethra and rectum | [159] |
n.a. | block of binding to syndecan-1 receptor | acidic pH | 293 FT, HeLa, SiHa, and HaCaT | [160] | |
L. vaginalis L. salivarius L. crispatus CCFM1339 | block of cell proliferation; maintenance of epithelial mucosal barrier integrity | L-lactic acid and H2O2; E-cadherin increase; MMP-9 decrease | HeLa and SiHa; mouse models | [161,162] | |
L. gasseri LGV03 | enhance innate immune system; reduce inflammation damage | IFN-α and IFN-β upregulation; IL-6, IL1β and IL-8 downregulation | Ect1/E6E7 | [163] | |
L. gasseri L. jensenii | cell viability; balanced cervical environment | optimal IFN-γ; low IL-17 | SiHa | [150] | |
L. crispatus L. iners | block of oncogenic progression | decrease of E6 and E7 expression | SiHa | [164] | |
HIV | L. crispatus L. jensenii L. acidophilus | direct virucidal effect; immunomodulation; block of cell susceptibility | H2O2 | CEM, mucosa | [48,53] |
L. crispatus | virion trapping | lactic acid (protonated uncharged) | cervicovaginal mucus | [165,166,167] | |
n.d. (metabolite mixture mimicking eubiotic conditions) | reduction of viral infectivity in undamaged epithelial mucosal barrier | protonated lactic acid and SCFA mediated upregulation of epithelial barrier integrity markers and block of inflammatory mediators (IL-6, IL-8, TNFα, RANTES, and MIP3α) | ectocervical, endocervical and vaginal cell lines | [41,168,169] | |
HSV-2 | L. crispatus | block of viral receptor binding | adhesion; microcolony formation | vaginal epithelial cells, Vero and HeLa | [170] |
L. brevis | reduced cell permissivity | cell wall | Vero | [171] | |
HSV-1 | L. crispatus L. gasseri | reduction of viral titer | cell-free supernatant | Vero and HeLa | [172] |
n.a. (pH conditions evaluation) | fusogenic glycoproteins inactivation | acidic pH | n.a. | [173,174] | |
n.a. (fresh, healthy mucus evaluation) | virion trapping | cervicovaginal mucus | ex vivo | [175] |
Infection | Participants | Probiotic(s) | Treatment | Study Type | Main Findings | Ref |
---|---|---|---|---|---|---|
HPV-LSIL | 54 women (32 years on average) | L. casei Shirota (Yakult) | One probiotic drink (2 × 109 CFU) per day for 6 months | Prospective controlled pilot study | Improved the resolution of cytological abnormalities | [253] |
BV/ vaginitis with concomitant HPV | 117 women (32 on average group1; 29 on average group2) | L. rhamnosus BMX 54 (NORMOGIN®) after treatment with metronidazole for 7 days or fluconazole for 2 days | Vaginal tablet (2 × 104 CFU), once a day for 10 days, once every 3 days for 20 days, then once every 5 days for 2 months (group1), or once a week for 5 months (group2) | Pilot, randomized trial | Decreased HPV-related cytological abnormalities in group 2; increased HPV clearance | [254] |
HR-HPV | 121 women (30–65 years) | L. rhamnosus GR-1 + L. reuteri RC-14 (U-relax ®) | Oral capsule (5.4 × 109 CFU) once a day until HPV negativization | Randomized double-blind, placebo-controlled trial | Decreased mildly abnormal and low-quality cervical smears | [255] |
HPV- ASCUS or LSIL | 35 women (18–65 years) | L. crispatus M247 | Oral, 90 days | Open, non-controlled study | Improved HPV clearance; favored shift to CST I status | [149] |
HR-HPV and/or LR-HPV | 160 women (30–64 years) | L. crispatus M247 | Oral, 12 months | Pilot, randomized controlled trial | Reduced HPV-related cytological anomalies | [256] |
HPV | 200 women (30 years on average) | Lacidophilin + rhIFN-α2b | Vaginal capsules, two at a time, the second night after rhIFN-α2b intervention, for 4 courses of treatment | Controlled pilot study | Decreased HPV-positive | [257] |
HIV | 115 women (18–45 years) | L. rhamnosus GR-1 + L. reuteri RC-14 | Oral capsule (2 × 109 CFU) twice a day for 25 weeks | Randomized, double-blind, placebo-controlled trial | Increased CD4+ count | [258] |
HIV | 20 subjects (18–65 years) | L. rhamnosus HN001 + B. lactis Bi-07 | Oral gel formulation (109 CFU) once a day for 16 weeks | Randomized, double-blind, controlled trial | Increased beneficial gut bacteria and reduced harmful ones; increased CD4+ count; decreased IL-6 levels (a marker of HIV-infected mortality) | [259] |
HIV | 21 subjects (47 years on average) | L. rhamnosus CAN-1 | One yogurt daily (109 CFU/mL) for 30 days | Randomized, double-blind, controlled study | Increased CD4+ count; increased in subjective energy and ability to perform daily ability score | [260] |
HIV | 48 subjects (39–53 years) | L. rhamnosus GG (Dicoflor 60) | Oral capsule (6 × 109 CFU) twice a day for 16 weeks | Prospective, clinical interventional trial | Decreased intestinal inflammation; decreased harmful gut bacteria | [261] |
HIV | 48 subjects (42 years on average) | L. casei Shirota | One probiotic drink (4 × 1010 CFU) per day for 12 weeks | Double-blind, placebo-controlled pilot study | No adverse effects; no differences in CD4+ counts between control and treated groups | [262] |
HIV | 71 subjects (50 years on average) | L. plantarum CECT7484 + L. plantarum CECT748 + P. acidilactici CECT7483 (i3.1probiotic formulation) | Oral powder (109 CFU/sachet) once a day for 30 days | Randomized, double-blind trial | Increased CD4+/CD8+ ratio | [263] |
HSV-2 | 60 women on the 14–16th week of pregnancy | L. crispatus LBV88 + L. rhamnosus LBV96 + L. gasseri LBC150 + L. jensenii LBV116 (Florium) | Oral capsule (2.5 × 109 CFU) twice a day for one week | Unspecified | Improved vaginal microbiota and vaginal discomfort; reduced complications related to pregnancy | [264] |
HSV-2 | 81 women (17–57 years) | L. brevis CD2 + L. brevis + KB290 + L. brevis SBC8803 | Vaginal capsule (2 × 109 CFU) twice a day for 6 months | Randomized double-blind controlled trial | Reduced the healing time of the lesions and the duration of viral shedding; suppressed recurrent herpes virus infection | [265] |
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Avitabile, E.; Menotti, L.; Croatti, V.; Giordani, B.; Parolin, C.; Vitali, B. Protective Mechanisms of Vaginal Lactobacilli against Sexually Transmitted Viral Infections. Int. J. Mol. Sci. 2024, 25, 9168. https://doi.org/10.3390/ijms25179168
Avitabile E, Menotti L, Croatti V, Giordani B, Parolin C, Vitali B. Protective Mechanisms of Vaginal Lactobacilli against Sexually Transmitted Viral Infections. International Journal of Molecular Sciences. 2024; 25(17):9168. https://doi.org/10.3390/ijms25179168
Chicago/Turabian StyleAvitabile, Elisa, Laura Menotti, Vanessa Croatti, Barbara Giordani, Carola Parolin, and Beatrice Vitali. 2024. "Protective Mechanisms of Vaginal Lactobacilli against Sexually Transmitted Viral Infections" International Journal of Molecular Sciences 25, no. 17: 9168. https://doi.org/10.3390/ijms25179168