Elemental sulfur enhances the anti-fungal effect of Lacticaseibacillus rhamnosus Lcr35.

Lacticaseibacillus rhamnosus Lcr35 is a well-known bacterial strain whose efficiency in preventing recurrent vulvovaginal candidiasis has been largely demonstrated in clinical trials. The presence of sodium thiosulfate (STS) has been shown to enhance its ability to inhibit the growth of Candida albicans strains. In this study, we confirmed that Lcr35 has a fungicidal effect not only on the planktonic form of C. albicans but also on other life forms such as hypha and biofilm. Transcriptomic analysis showed that the presence of C. albicans induced a metabolic adaptation of Lcr35 potentially associated with a competitive advantage over yeast cells. However, STS alone had no impact on the global gene expression of Lcr35, which is not in favor of the involvement of an enzymatic transformation of STS. Comparative HPLC and gas chromatography-mass spectrometry analysis of the organic phase from cell-free supernatant (CFS) fractions obtained from Lcr35 cultures performed in the presence and absence of STS identified elemental sulfur (S0) in the samples initially containing STS. In addition, the anti-Candida activity of CFS from STS-containing cultures was shown to be pH-dependent and occurred at acidic pH lower than 5. We next investigated the antifungal activity of lactic acid and acetic acid, the two main organic acids produced by lactobacilli. The two molecules affected the viability of C. albicans but only at pH 3.5 and in a dose-dependent manner, an antifungal effect that was enhanced in samples containing STS in which the thiosulfate was decomposed into S0. In conclusion, the use of STS as an excipient in the manufacturing process of Lcr35 exerted a dual action since the production of organic acids by Lcr35 facilitates the decomposition of thiosulfate into S0, thereby enhancing the bacteria's own anti-fungal effect.

The impact of the Fungus-Host-Microbiota interplay upon Candida albicans infections: current knowledge and new perspectives.

Candida albicans is a major fungal pathogen of humans. It exists as a commensal in the oral cavity, gut or genital tract of most individuals, constrained by the local microbiota, epithelial barriers and immune defences. Their perturbation can lead to fungal outgrowth and the development of mucosal infections such as oropharyngeal or vulvovaginal candidiasis, and patients with compromised immunity are susceptible to life-threatening systemic infections. The importance of the interplay between fungus, host and microbiota in driving the transition from C. albicans commensalism to pathogenicity is widely appreciated. However, the complexity of these interactions, and the significant impact of fungal, host and microbiota variability upon disease severity and outcome, are less well understood. Therefore, we summarise the features of the fungus that promote infection, and how genetic variation between clinical isolates influences pathogenicity. We discuss antifungal immunity, how this differs between mucosae, and how individual variation influences a person's susceptibility to infection. Also, we describe factors that influence the composition of gut, oral and vaginal microbiotas, and how these affect fungal colonisation and antifungal immunity. We argue that a detailed understanding of these variables, which underlie fungal-host-microbiota interactions, will present opportunities for directed antifungal therapies that benefit vulnerable patients.

Comparative phase I randomized open-label pilot clinical trial of Gynophilus® (Lcr regenerans®) immediate release capsules versus slow release muco-adhesive tablets.

Gynophilus® (Lcr regenerans®) is a live biotherapeutic product (LBP) that contains the live biotherapeutic microorganism Lactobacillus rhamnosus Lcr35®, which is indicated to restore vaginal health. The aim of the study was to compare the safety, ease of use, and compliance of two formulations (immediate release: IR capsule and slow release: SR muco-adhesive tablets) as well as the colonization of Lcr35® in healthy women. This phase I study (Comprigel) is a parallel, randomized, 4-arm, and open-label clinical trial evaluating an IR daily capsule formulation vs. a SR tablet administered every 3, 4, or 5 days for 21 days. Self-collected vaginal swabs were used to quantify Lcr35® and characterize the composition and structure of the vaginal microbiota. Both LBPs were well-tolerated, and no severe adverse effects were reported. All groups had Lcr35® vaginal concentrations over 107 colony forming unit per milliliter of vaginal secretion on each day in the study. The new Gynophilus® slow release tablets administered either every 3, 4, or 5 days provided vaginal concentrations that were not significantly different from those of classic Gynophilus® (capsule) once-a-day regimen. The LBPs and the different regimens did not adversely influence the abundance of native Lactobacillus spp. and indeed tended to favor their growth and reduce colonization by non-Lactobacillus spp. This study illustrates that the SR muco-adhesive LBP tablet (Gynophilus® SR) administered every 3 or 4 days as a safe, well-tolerated, and efficacious alternative to a more demanding IR daily capsule and could protect women's healthy vaginal microbiome by promoting endogenous Lactobacillus spp.