Lactobacillus probiotics restore vaginal and gut microbiota of pregnant women with vaginal candidiasis.

The development of probiotics has now included the areas along the gut-vaginal axis. We thus aimed to investigate the effects of lactobacilli probiotic to modulate and restore vaginal and gut microbiota of pregnant women with vaginal candidiasis (VC). A randomised, double-blind and placebo-controlled study was performed in 78 pregnant women with VC. Patients were randomised to either the probiotic (SynForU-HerCare) or placebo which were administered at baseline and continued for 8-weeks (two capsules/day of 9.5 log cfu/capsule). Microbiota profiles were assessed at time points of weeks-0, 4 and 8 for high vaginal swab and faecal samples. Shannon diversity index showed that after 8-weeks amid VC, a shift in microbial community compositional changes occurred in the high vaginal region at both genus (P=0.025) and species (P=0.044) levels, where the administration of probiotic prevented such a shift. These changes were mainly attributed to a decreased in abundance of Lactobacillus (P=0.042) accompanied by increased abundance of Prevotella (P=0.002) and Atopobium (P=0.002) in the placebo group while the probiotic group remained unchanged over time. The administration of probiotics also prevented a reduced abundance of faecal phylum Firmicutes after 8-weeks as seen in the placebo group (P<0.0001), which also showed reduction at subsequent taxonomic levels of class, family, genera and species. VC has not only altered the microbiota of vagina regions but also gut microbiota profiles, causing lessening of gut microbiota that are crucial for gut nutrient availability, protection and immunity. The administration of lactobacilli probiotics has prevented such a shift, leading to better modulated gut and vaginal microenvironment amid VC. The study was registered at ClinicalTrials.gov: identifier number NCT03940612.

Lactobacilli reduce recurrences of vaginal candidiasis in pregnant women: a randomized, double-blind, placebo-controlled study.

AIMS: The aim of this study was to investigate the effects of lactobacilli strains in preventing the recurrences of vaginal candidiasis (VC) in 78 pregnant women with VC (lactobacilli, n = 39; placebo, n = 39) and the potential benefits on quality of life. METHODS AND RESULTS: The lactobacilli putative probiotic (SynForU-HerCare; two capsules/day of 9·5 log CFU per capsule) or placebo was administered for 8-weeks in a randomized, double-blind, placebo-controlled study. Subjects were assessed for vaginal and gut health conditions at baseline, week-4 and week-8 via questionnaires. The vulvovaginal symptom questionnaire not only covered aspects pertaining to vulvovaginal symptoms but also the quality of life impacts such as emotional, social and sexual. The administration of lactobacilli reduced symptoms of irritation (P = 0·023) and discharge (P = 0·011) starting week-4 and continued after week-8 (P < 0·05), accompanied by reduced symptoms for burning after week-8 (P = 0·046) as compared to the placebo. Patients consuming lactobacilli also showed reduced concern about symptoms after week-4 (P = 0·010) and continued after week-8 (P = 0·001), accompanied by reduced impairment of daily activities attributed to vulvovaginal symptoms (P = 0·012) and continued after week-8 (P = 0·026). Insignificant differences were observed for sexual impacts between treatment groups. The administration of lactobacilli also reduced recurrences of both emotional and social stress as compared to the placebo at both week-4 and week-8 (P < 0·05). Patients consuming lactobacilli showed higher defecation times per week at week-4 (P = 0·010) and week-8 (P = 0·001) as compared to the placebo group, indicating the potential to reduce risks of pregnancy-induced constipation. CONCLUSIONS: Lactobacilli probiotics are beneficial towards pregnant women, especially in reducing vulvovaginal symptoms and recurrences of VC, accompanied by improved emotional and social distress attributed to VC. SIGNIFICANCE AND IMPACT OF THE STUDY: The study demonstrated the preventive and modulatory roles of lactobacilli strains against VC in pregnant women. Taken altogether, our present data illustrated that lactobacilli probiotics are beneficial towards pregnant women, especially in reducing vulvovaginal symptoms and recurrences of VC, accompanied by improved emotional and social distress attributed to VC, thus could be a potential strategy for the maintenance of vaginal health during pregnancy.

Recovery of Lactobacillus casei strain Shirota (LcS) from faeces of healthy Singapore adults after intake of fermented milk.

To validate survival of Lactobacillus casei strain Shirota (LcS) during passage through the gastrointestinal tract of healthy Singaporean young adults, 21 participants (18-25 years old) were asked to consume a 100 ml of fermented milk drink containing 1.0×108 cfu/ml of LcS daily for 14 days, and to maintain their dietary habit and life style. During and at the end of the ingestion period, both culture method (identity confirmed by ELISA) and 16s rRNA sequencing results revealed that viable LcS (7.27 and 7.64 log10 cfu/g of faeces at the ingestion period Day 7 and Day 14, respectively) and Lactobacillus could be recovered from the faeces of all the subjects. The viable LcS count from male and female were comparable for each time point. Before consumption (baseline) and 14 days after cessation of consumption of the fermented milk, LcS was not detected in most of the subjects. In this study condition, the composition of the major gut microbiota (>0.1% in relative abundance of genus) and characteristics of defaecation such as stool consistency and frequency of defecation did not change throughout the study before and after ingestion of LcS. LcS was able to survive passage through the gastrointestinal tract of Singapore adults without sustainable colonisation, but the effect of LcS on microbiota modulation, stool consistency and frequency was not observed under this study condition.

The Plasmodium PI(4)K inhibitor KDU691 selectively inhibits dihydroartemisinin-pretreated Plasmodium falciparum ring-stage parasites.

Malaria control and elimination are threatened by the emergence and spread of resistance to artemisinin-based combination therapies (ACTs). Experimental evidence suggests that when an artemisinin (ART)-sensitive (K13 wild-type) Plasmodium falciparum strain is exposed to ART derivatives such as dihydroartemisinin (DHA), a small population of the early ring-stage parasites can survive drug treatment by entering cell cycle arrest or dormancy. After drug removal, these parasites can resume growth. Dormancy has been hypothesized to be an adaptive physiological mechanism that has been linked to recrudescence of parasites after monotherapy with ART and, possibly contributes to ART resistance. Here, we evaluate the in vitro drug sensitivity profile of normally-developing P. falciparum ring stages and DHA-pretreated dormant rings (DP-rings) using a panel of antimalarial drugs, including the Plasmodium phosphatidylinositol-4-OH kinase (PI4K)-specific inhibitor KDU691. We report that while KDU691 shows no activity against rings, it is highly inhibitory against DP-rings; a drug effect opposite to that of ART. Moreover, we provide evidence that KDU691 also kills DP-rings of P. falciparum ART-resistant strains expressing mutant K13.

Minimizing DILI risk in drug discovery - A screening tool for drug candidates.

Drug-induced liver injury (DILI) is a leading cause of acute hepatic failure and a major reason for market withdrawal of drugs. Idiosyncratic DILI is multifactorial, with unclear dose-dependency and poor predictability since the underlying patient-related susceptibilities are not sufficiently understood. Because of these limitations, a pharmaceutical research option would be to reduce the compound-related risk factors in the drug-discovery process. Here we describe the development and validation of a methodology for the assessment of DILI risk of drug candidates. As a training set, 81 marketed or withdrawn compounds with differing DILI rates - according to the FDA categorization - were tested in a combination of assays covering different mechanisms and endpoints contributing to human DILI. These include the generation of reactive metabolites (CYP3A4 time-dependent inhibition and glutathione adduct formation), inhibition of the human bile salt export pump (BSEP), mitochondrial toxicity and cytotoxicity (fibroblasts and human hepatocytes). Different approaches for dose- and exposure-based calibrations were assessed and the same parameters applied to a test set of 39 different compounds. We achieved a similar performance to the training set with an overall accuracy of 79% correctly predicted, a sensitivity of 76% and a specificity of 82%. This test system may be applied in a prospective manner to reduce the risk of idiosyncratic DILI of drug candidates.

In-situ monitoring of the thermal desorption of alkanethiols with surface plasmon resonance spectroscopy (SPRS).

Thermal desorption investigations on self-assembled monolayers (SAMs) had previously been carried out using techniques such as thermal desorption spectroscopy (TDS), scanning tunneling microscopy (STM) and X-ray photo-electron spectroscopy (XPS). In this paper, the thermal dissociation of alkanethiols (CnH(2n + 1)SH) at various chain lengths (n= 6, 12, 18) on sputtered gold layers was monitored in-situ using the Kretschmann surface plasmon resonance configuration on a spectroscopic ellipsometer. We found that the longest alkanethiol (C18) exhibits the greatest thermal stability, manifested by the least amount of angular shift, during heating, in the resonant spectral features. Predictions of desorption temperatures from SPRS for the longer chain thiols are in good agreement with XPS measurements.