Metabolic origins of urogenital malodour in women and their relationship with their microbiota: can probiotics help?
Abstract
The objectives of this thesis were to characterize the biochemical origins of malodour in the female bladder, elucidate how vaginal Lactobacillus species interact with malodorous compounds and assess the potential to deliver probiotic strains topically.
Metabolomic tools were used to explore differences between the urine of healthy women and those positive for Escherichia coli urinary tract infection (UTI). Positive samples had increased concentrations of the fishy-smelling biogenic amine (BA) trimethylamine (TMA). The BAs cadaverine, putrescine, and tyramine, causatives of malodour in bacterial vaginosis (BV) were also quantified. Putrescine was elevated in BV samples. In vitro, the capacity of five uropathogenic E. coli strains to produce the four BAs of interest was tested. When grown in human urine, E. coli was shown to produce putrescine and TMA, and also biosynthesize cadaverine which, might be produced under specific conditions in some patients. This confirmed that there is an overlap in the malodorous compounds present in the urogenital tract of women with BV and UTI, two highly prevalent conditions driven by dysbiosis.
The same metabolomic approaches were used to characterize clinical strains of Lactobacillus crispatus, an abundant species in the healthy vagina. There were no differences in terms of BA profiles between those isolated from Lactobacillus dominated microbiotas and those from a dysbiotic vagina. The latter had higher inhibitory activity towards common uropathogens, potentially due to metabolic adaptation.
The amine-degradation capacity of L. crispatus was further characterized and previous exposure to BAs led to higher tolerance. Tests with cell-free extracts revealed that bacterial metabolites alone can reduce the amount BAs. Some strains were able to degrade BAs, while others were found produce them.
In order to assess the feasibility that malodour-reducing lactobacilli could be placed in a topical preparation for delivery to the perineal and vulval skin, four different oils were assessed. Coconut oil and petroleum jelly emerged as the best candidates for retention of viability.
It is our hope that these findings will help to develop probiotic-based products that not only restore homeostasis, but also treat the malodour that impairs a woman’s quality of life.