Page 47 - JCTR-11-5

Journal of Clinical and
Translational Research Vaginal microbiota in menopause pathologies

cancer, though establishing direct causality remains such as C. trachomatis and N. gonorrhoeae, increase
challenging due to the complex interplay of multiple the risk of ovarian cancer, as well as viral infections
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contributing factors and the high variability of individual such as HPV, cytomegalovirus, Epstein-Barr virus, and
microbiomes. 88 HIV. 26,56,84 In addition, antibodies against C. trachomatis
Hormonal influences such as not having given birth, may be associated with a higher risk of ovarian cancer
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early onset of menstruation, and late menopause are by promoting the survival of cells with damaged DNA.
associated with an elevated risk. In contrast, pregnancy Some microorganisms invade the tumor, generating an
and oral contraceptive use offer protective effects by “intratumoral microbiota” that contributes to cancer
limiting ovulatory cycles. Oral contraceptives also progression through mutations in DNA, activation of
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carcinogenic pathways, and metastasis. Certain bacterial
influence the expression of transforming growth factor
β isoforms, triggering apoptosis in ovarian epithelial components, including E. coli lipopolysaccharide found
cells. Environmental exposures, including diets high in the VM, can trigger pro-inflammatory cytokine
in animal fats and Westernized lifestyles, may increase production, which supports tumor progression and
resistance to chemotherapy. Inflammation within the
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susceptibility, while diets rich in vegetables are linked to genital tract has been linked to carcinogenesis, as seen
reduced risk. Genetically, although most ovarian cancer 56
cases are sporadic, about 10% are inherited. Mutations in PID, a recognized risk factor for ovarian cancer. An
in the BRCA1 and BRCA2 genes are major contributors, imbalance in the VM—marked by a decline in Lactobacillus
conferring a 20–40% lifetime risk for BRCA1 mutation species and an increase in genera such as Acinetobacter,
Burkholderia, G. vaginalis, and Prevotella—may promote a
carriers and a 10–20% for BRCA2 carriers. Having local environment prone to inflammation and malignancy.
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multiple pregnancies, undergoing tubal ligation, or using This alteration appears to be associated with metabolic
oral contraceptives has been shown to lower the risk of
ovarian cancer. 56 shifts involving glycerophospholipids and tryptophan,
which, in murine models, contribute to ovarian tumor
10.3.2. Oncobiome or the interaction between the development. 56,96 Local inflammation, induced by bacterial
human microbiome and carcinogenesis colonization, can promote carcinogenesis by activating
pattern recognition receptors such as TLR2, 4, and 5,
The concept of oncobiosis refers to the interplay between which respond to Gram-negative bacteria. The activation
the human microbiome and the development of cancer, and of these receptors triggers inflammation through signaling
it has been observed in several anatomical sites, including pathways like NF-κB, which favors oncogenesis. Tumor-
the vaginal and cervicovaginal regions, the upper genital associated macrophages are essential for the development
tract, ovaries, tumor tissue, peritoneal cavity, bloodstream, of ovarian cancer, and peritoneal colonization can
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and fecal matter. This microbial imbalance is linked to drive metastasis formation, including interaction with
a reduction in microbial diversity, particularly in the the intestinal microbiome, promoting spread to the
peritoneal and intratumoral microbiomes found in ovarian gastrointestinal tract. 56,88 Moreover, the microbiome
cancer cases. 88,89 Analyses of tumor specimens revealed a affects the response to treatments such as chemotherapy.
predominance of bacterial phyla such as Proteobacteria Modifying the microbiome with antibiotics, probiotics,
and Firmicutes compared to non-cancerous tissues. 88-91 and nutrients could be a promising therapeutic and
These microbes can secrete genotoxins like colibactin and diagnostic strategy. 89
cytotoxic distending toxins, which cause DNA damage
and trigger repair mechanisms. Moreover, a decrease 10.3.3. Summary
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in microbial diversity has been observed in cancer cases, Research on the microbiota and ovarian cancer has
suggesting that changes in the microbiota could influence identified a significant relationship between microbial
disease development. 26,88,91 On the other hand, a study alteration and disease progression. Dysbiosis affects
revealed that malignant epithelial ovarian tumors harbored areas such as the vagina, genital tract, tumor tissue, and
a more diverse and abundant microbiota, including intestines, contributing to the initiation and progression
members of the order Actinomycetales as well as genera of cancer. Bacteria such as Proteobacteria and Firmicutes
such as Acinetobacter, Streptococcus, Ochrobacterium, and predominate in these tissues, and bacterial infections
Pseudomonas. They also identified that P. acnes might such as C. trachomatis and N. gonorrhoeae increase cancer
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accelerate cancer development. risk. The reduction of Lactobacillus in women with BRCA
In the vagina, a low abundance of Lactobacillus is mutations may be a key factor. Bacterial metabolites induce
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associated with ovarian cancer and BRCA mutations, chronic inflammation, suggesting the use of probiotics and
especially in younger patients. Genital infections, antibiotics as potential treatments.
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Volume 11 Issue 5 (2025) 41 doi: 10.36922/JCTR025150016