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Abstract The human microbiome contains genetic information that regulates metabolic processes in response to host health and disease. While acidic vaginal pH is maintained in normal conditions, the pH level increases in infectious vaginitis. We propose that this change in the vaginal environment triggers the biosynthesis of anti-vaginitis metabolites. Gene expression levels of Chryseobacterium gleum, a vaginal symbiotic bacterium, were found to be affected by pH changes. The distinctive difference in the metabolic profiles between two C. gleum cultures incubated under acidic and neutral pH conditions was suggested to be an anti-vaginitis molecule, which was identified as phenylacetic acid (PAA) by spectroscopic data analysis. The antimicrobial activity of PAA was evaluated in vitro, showing greater toxicity toward Gardnerella vaginalis and Candida albicans, two major vaginal pathogens, relative to commensal Lactobacillus spp. The activation of myeloperoxidase, prostaglandin E2, and nuclear factor-κB, and the expression of cyclooxygenase-2 were reduced by an intravaginal administration of PAA in the vaginitis mouse model. In addition, PAA displayed the downregulation of mast cell activation. Therefore, PAA was suggested to be a messenger molecule that mediates interactions between the human microbiome and vaginal health.

Purpose: Infertility affects 10% to 15% of couples, and male factor accounts for 50% of the cases. The relevant male genetic factors, which account for at least 15% of male infertility, include Y-chromosome microdeletions. We investigated clinical data and patterns of Y-chromosome microdeletions in Korean infertile men. Materials and Methods: A total of 919 infertile men whose sperm concentration was ≤5 million/mL in two consecutive analyses were investigated for Y-chromosome microdeletion. Among them, 130 infertile men (14.1%) demonstrated Y-chromosome microdeletions. Medical records were retrospectively reviewed. Results: In 130 men with Y-chromosome microdeletions, 90 (69.2%) had azoospermia and 40 (30.8%) had severe oligozoospermia. The most frequent microdeletions were in the azoospermia factor (AZF) c region (77/130, 59.2%), followed by the AZFb+c (30/130, 23.1%), AZFa (8/130, 6.2%), AZFb (7/130, 5.4%), AZFa+b+c (7/130, 5.4%), and AZFa+c (1/130, 0.7%) regions. In men with oligozoospermia, 37 (92.5%) had AZFc microdeletion. Chromosomal abnormalities were detected in 30 patients (23.1%). Higher follicle-stimulating hormone level (23.2±13.5 IU/L vs. 15.1±9.0 IU/L, p

Accumulating evidence indicates that microbial communities in the human body crucially affect health through the production of chemical messengers. However, the relationship between human microbiota and cancer has been underexplored. As a result of a biochemical investigation of the commensal oral microbe, Corynebacterium durum, we identified the non-enzymatic transformation of tryptamine into an anticancer compound, durumamide A (1). The structure of 1 was determined using LC-MS and NMR data analysis as bis(indolyl)glyoxylamide, which was confirmed using one-pot synthesis and X-ray crystallographic analysis, suggesting that 1 is an oxidative dimer of tryptamine. Compound 1 displayed cytotoxic activity against various cancer cell lines with IC50 values ranging from 25 to 35 μM. A drug affinity responsive target stability assay revealed that survivin is the direct target protein responsible for the anticancer effect of 1, which subsequently induces apoptosis-inducing factor (AIF)-mediated apoptosis. Inspired by the chemical structure and bioactivity of 1, a new derivative, durumamide B (2), was synthesized using another indole-based neurotransmitter, serotonin. The anticancer properties of 2 were similar to those of 1; however, it was less active. These findings reinforce the notion of human microbiota-host interplay by showing that 1 is naturally produced from the human microbial metabolite, tryptamine, which protects the host against cancer.