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Thesis Format

Integrated Article

Degree

Doctor of Philosophy

Program

Microbiology and Immunology

Supervisor

Reid, Gregor

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.

Summary for Lay Audience

Yearly, millions of women seek medical advice due to vaginal and urinary foul smell. The most common causes are bacterial vaginosis (BV) and urinary tract infection (UTI). Antibiotics are prescribed but can take several days to provide relief from the odour. This is a major burden for patients and takes a toll on their life quality. A healthy vagina has its own collection of microbes with the most abundant being lactobacilli. They use the nutrients within the vagina and, in exchange, provide protection to the host primarily by not allowing the establishment of harmful microbes. When lactobacilli reserves are reduced there are increased chances of infection. Some probiotics (‘live bacteria that, when taken in adequate amounts, confer a health benefit on the host’), such as Lacticaseibacillus rhamnosus GR-1 and Limosilactobacillus reuteri RC-14, are used to help maintain equilibrium within the vagina, thus, preventing recurrence of infection. We propose that certain probiotics could be used, alone or in combination with antibiotics, to target malodour, thereby providing relief sooner. However, not all probiotics are the same and thorough screening must be carried out to select ones with specific malodour reducing characteristics. Here, we investigated compounds known as biogenic amines, which are the culprits of fishy vaginal and urinary smell. We found that patients with UTI have large quantities of these chemicals in their urine. We also identified that certain lactobacilli that are common in the vagina can degrade these compounds. We suggest the direct application of probiotics through a cream or ointment, such as petroleum jelly or coconut oil, could allow women to self-manage malodour. Overall, the findings compiled in this thesis provide a basis for the probiotic industry to develop products that can combat a major reason for women to seek medical care.

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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