Abstract
GYNOPHILUS (Lcr REGENERANS) is a live biotherapeutic product (LBP) aimed at restoring the vaginal microbiome and contains the live biotherapeutic microorganism Lactobacillus rhamnosus Lcr35. In this study, the LBP formulation and manufacturing process significantly enhanced the anti-Candida activity of L. rhamnosus Lcr35, with a complete loss of viability of the yeast after 48 h of coincubation. Sodium thiosulfate (STS), one excipient of the product, was used as a potentiator of the anti-Candida spp. activity of Lactobacilli. This contact-independent phenomenon induced fungal cell disturbances, as observed by electron microscopy observations. Nonverbal sensory experiments showed clear odor dissimilarities between cocultures of L. rhamnosus Lcr35 and C. albicans in the presence and absence of STS, suggesting an impact of odor-active metabolites. A volatolomic approach allowed the identification of six odor-active compounds, including one sulfur compound that was identified as S-methyl thioacetate (MTA). MTA was associated with the antifungal effect of Lcr35, and its functional link was established in vitro. We show for the first time that the LBP GYNOPHILUS, which is a highly active product in the reduction of vulvovaginal candidiasis, requires the presence of a sulfur compound to fully achieve its antifungal effect.
Highlights
GYNOPHILUS (Lcr REGENERANS) is a live biotherapeutic product (LBP) aimed at restoring the vaginal microbiome and contains the live biotherapeutic microorganism Lactobacillus rhamnosus Lcr[35]
C. albicans ATCC 10231 viability was reduced by 2.7 log[10] (CFU/ml) after 48 h as compared to the non-treated control (Fig. 1) without any impact onto Lcr[35] viability (Fig. 1a)
live biotherapeutic microorganisms (LBM) are often administered as complex manufactured formulated products and positive impacts of the manufacturing process have been previously demonstrated in several studies[22,23,24]
Summary
GYNOPHILUS (Lcr REGENERANS) is a live biotherapeutic product (LBP) aimed at restoring the vaginal microbiome and contains the live biotherapeutic microorganism Lactobacillus rhamnosus Lcr[35]. Vulvovaginal candidiasis (VVC) is the most common vaginal pathology associated with the presence of Candida spp. and it affects 70–75% of women at least once in their live[1,2]. GYNOPHILUS (Lcr REGENERANS) LBP contains Lactobacillus rhamnosus Lcr[35], a LBM whose in vitro and in vivo characteristics are well-documented[11,12,13,14,15] This LBP is recommended in preventive and curative therapies for gynecological indications, mostly vulvovaginal c andidiasis[16,17,18]. Galenic vaginal forms, LBP GYNOPHILUS, were shown to impair the growth of C. albicans and to induce a fungicidal effect after 24 h of co-incubation[22]
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