Study: Lactobacillus Crispatus and bacterial vaginosis

This article is part of our special edition "Immune Health" from October 2022. Load the full edition here down .

study goal

Investigation of the effect of a living biotherapeutic vaginal ingredient l Crispatus CTV-05 (Lactin-V) on genital immunology and important vaginal bacteria

Key to take away

This study suggests that the vaginal application of Lactin-V is associated with a continued reduction in mucosal inflammation and possibly an improved mucosal barrier function.

design

A sub-study of a randomized, placebo-controlled phase 2B study with Lactin-V to reduce the recurrence of bacterial vaginosis

participant

For the original study, 228 women (at the age of 18–45) were recruited to take part in a phase 2b study with Lactin-V to reduce the recurrence of bacterial vaginosis. The sub-group of the study examined here comprised 66 women with a high loyalty to therapy, which were accidentally selected from the original study (32 in the Lactin V group; 34 in the placebo group). The average age was 33 years.

None of the women became positive for the human immune deficiency virus (HIV), syphilis, Neisseria gonorrhoeae , chlamydia trachomatis or trichomonas vaginalis . Pregnancy and urinary tract infection were negative in women. The characteristics and the sexual behavior of the participants at the beginning, including the latest sexual intercourse and the application of hormonal contraceptives as well as ethnicity, do not differ significantly between the groups. Women were eligible to participate who met at least three out of four clinical clinical criteria for bacterial vaginosis and had an nugent score of 4 to 10 due to the Gram coloring.

intervention

All participants received a 5-day cure with a vaginal metronidazole 0.75 % gel. After this treatment, they received either Lactin-V or a placebo, which was used vaginally for five days a day and then twice a week for five days in the first week. Job examinations took place 4, 8, 12 and 24 weeks after the registration.

lactobacillus crispatus CTV-05 (Lactin-V) is a living biotherapeutic product that contains a naturally occurring tribe of l crispatus . Lactin-V consists of a powder with 2 x 10 9 Coloning units of l Crispatus CTV-05 is preserved with inactive ingredients and is administered via a pre-filled applicator.

study parameters

The researchers examined soluble immune factors and the absolute frequency of bacterial taxa using multiplex-elisa and quantitative polymerase chain reaction (PCR).

primary result

The primary results were the vaginal concentrations of interleukin 1 alpha (IL-1A) and soluble e-cadher after 24 weeks (i.e. 13 weeks after the end of the treatment, regardless of whether Lactin-V or placebo).

More results were the vaginal concentrations of soluble immune factors and the absolute frequency of important vaginal bacteria, including l crispatus , l crispatus stem CTV-05, liner , l jensenii , l Gassi , Vaginalis , atopobium vaginae , megasphaera species and Prevotella Spezies.

most important knowledge

The treatment with lactin-V was associated with significantly lower concentrations of the pro-inflammatory cytokins IL-1A ( p = 0.042), an inflammatory, and soluble e-cadherin ( p = 0.035), a biomarker for the disturbance of the epithelial barrier.

In addition, Lactin-V was connected to increased concentrations of induced protein 10 (IP-10) after 23 weeks after 23 weeks. Interferon (IFN) Alpha 2a and IL-17A were not detectable in more than 50 % of the samples. The detection of IFN-Alpha 2a or IL-17A was not significantly connected to the treatment.

transparency

This study was financed by the Canadian Institutes of Health and Research and the National Institutes of Health (NIH) and the National Institute of Allergy and InfectIous Diseases (Niaid). One of the authors of this study, CR Cohen, MD, is the chairman of the scientific advisory board of Osel, the biotherapeutic company, the product pipeline lactin-V. He reports on grants from the Niaid and the NIH National Institute of Child Health and Human Development. He holds stock options for Osel and Evvy. Another author, B Coburn, PhD, reports on grants from the Western Foundation, the Canadian Institutes of Health Research, the Canadian Cancer Society, the McLaughlin Foundation, the National Cancer Institute and the Cystic Fibrosis Foundation as well as research income from Nubiyota, a company for microbiom therapy With a focus on development of new-like microbiota base for restoring intestinal equilibrium. Co-author R Kaul reports on a scholarship from the Canadian Institutes of Health Research.

implications and restrictions for practice

bacterial vaginosis (BV) affects 15 to 50 % of women of childbearing age 1 The recurrence rate is quite problematic, and even after treatment with an indexed antibiotic, 20 to 75 % of women within 3 months occur. (STIS), including HIV, as well as for premature births. ^{3 BV also leads to negative emotional, sexual and social effects and represents an economic burden for patients. If we could reduce the risk of renewed occurrence or even promote primary prevention, we would help find an urgently needed solution to the health of women.}

I will immediately go into the study implications and restrictions of the current study, but let's take a look at the original study from which the current sub -study emerged. I believe that this study has a greater impact on practice. The original study (Cohen et al., nejm , 2020) included a phase 2b study to assess whether treatment with lactin-V after vaginal administration of metronidazole against BV lowered the incidence of BV again. Women between the ages of 18 and 45 with BV completed a 5-day cure with a vaginal metronidazole gel (0.75 %). Within 48 hours after completing this treatment, they were randomized to a vaginal administration of lactin-V for 11 weeks compared to placebo. During this procedure, the participants had to introduce an applicator for five days every evening and then twice a week. The primary result was the percentage of women, in which a re -occurrence of BV occurred in week 12. The researchers randomized 228 women, 152 of them in the treatment group and 76 in the placebo group. In week 12, the BV recurrence in the Lactin V group was significantly lower, with a recurrence rate of 30 % in the Lactin V group (compared to a recurrence rate of 45 % in the placebo group) and with a persistent effect in the Lactin V group in week 24.

The recurrence rate is quite problematic, and even after treatment with an indicated antibiotic, 20 to 75 % of women occur in a recurrence within 3 months.

Now to our current sub -study, which led to a sustainable reduction in genital inflammation and a biomarker for the integrity of the epithelium. Lactin-V was associated with the concentration of soluble immune factors and a wealth of several bacterial taxa, which is a good sign of genital immunity. These persistent genital immune effects were conveyed primarily by a reduced amount of bacterial vaginosis-associated taxa Prevotella SPP and megasphaera SPP and to a lesser extent an increased amount of it l Crispatus . There are strong relationships between the vaginal microbiota and the HIV risk, which indicates that a dominance of the vaginal microbiota is promoted l Crispatus in the vagina could reduce the HIV risk.

women with l crispatus women with a supremacy in their vaginal ecosystem also have fewer transitions to microbiota of type bacterial vaginosis than women with other lactobacillus dominating species, such as z liner . This indicates l crispatus , inflammatory bacterial vaginosis-associated bacteria can inhibit or exclude. This is partially conveyed by the production of lactic acid and antimicrobial metabolites. We have other evidence that prove the l crispatus is an important lactic acid producer in the vagina.

There are some restrictions on the study. The researchers judged sexually transmitted diseases only in the first screening and only tested them again if the women had symptoms. The stage of the menstrual cycle was not recorded, unless the women had their menstruation. A fluctuation in normal sex hormones is a potential factor for genital immunology and pH value. The tests used were a targeted QPCR and not a 16SrRNA gene sequencing, which restricted the ability to evaluate vaginal microbiota and to identify contributions from other microbes. Only US women took part in the study, although it was an ethnically heterogeneous cohort.

disclosure of conflicts of interest

dr. Tori Hudson is a co-owner of a company for nutritional supplements for women, Vitanica, which offers a wide range of health, nutritional and herbal products for women, including probiotic species and tribes for oral and vaginal use to prevent and treat urogynecological diseases. She is also a medical consultant for nutritional fundamental for health, symphony, integrative therapeutics and Gaia Herbs Pro.