Sometimes called uterine cancer, endometrial cancer begins in the layer of cells lining the uterus. Due to emerging evidence that the uterus is not a sterile cavity, researchers have begun to investigate the endometrial microbiome and its possible role in endometrial cancer.
Endometrial cancer, in brief
The endometrium is dynamic tissue, responding to estrogen and progesterone by thickening in preparation to nourish a fetus and shedding (menstruation) each month when not needed.
Endometrial cancer risk is increased by advanced age, early onset of menses, late menopause, nulliparity (no births), obesity, postmenopausal estrogen therapy, and a family history of certain cancers. While the prognosis is good, endometrial cancer struck more than 417,000 new women globally in 2020.
Genetic mutations are often the cause of endometrial cancer, which has been traditionally classified into Type I and Type II, differentiated by characteristics, prognosis, and treatment. Over the last decade, more diverse schemes have been suggested.
In addition, environmental factors play a part in the cancer’s origins. Excess exposure to hormones as well as metabolic disorders such as obesity can increase risk. It does not appear that human papillomavirus (HPV) is a risk factor for endometrial cancer though there are some contradictory results.
Another important part of the uterine environment is the microbiome.
A few studies have characterized the microbiome composition in the endometrium. Whereas some have found that Lactobacillus is the dominant genus, others have suggested that non-Lactobacillus species are more common in the endometrium. Notably, most of the women involved were undergoing hysterectomies or other procedures for uterine disorders or irregularities. One study with a healthy control group identified Lactobacillus, Gardnerella, Bifidobacterium, Streptococcus, and Alteromonas as higher in the healthy group when compared with the group presenting with endometrial polyps or chronic endometriosis.
Microbiome in endometrial cancer
The composition of endometrial microbiota in endometrial cancer is not clear. Some studies point to decreased diversity while others observe that the risk factors for endometrial cancer (post-menopause, obesity, and high vaginal pH) increase the diversity of endometrial microbiota. Significantly, Porphyromonas somerae has been identified as the most abundant organism in patients with endometrial cancer.
In a complex bidirectional relationship, the microbiome is connected to endometrial cancer in several ways:
An excess of estrogen in the body is an important risk factor for endometrial cancer. Enteric bacterial genes—called the estrobolome— produce products that are capable of metabolizing estrogens. Consequently, estrobolome dysbiosis can lead to an estrogen increase, contributing to the early stages of endometrial cancer formation as well as its risk factors.
Porphyromonas somerae and other pathogens in the endometrium induce the production of pro-inflammatory cytokines, which are involved in endometrial carcinogenesis.
Response to treatment
The microbiome is also involved in the body’s response to treatment. The microbiome may possibly be exploited to reduce the toxicity induced by antitumor therapies (chemotherapy, radiation, and immunotherapy) and improve the response to these therapies.
In turn, the microbiota may be altered by treatment.
Modulation of the endometrial microbiome
Altering the endometrial microbiome may provide a novel and safe method to reduce risk factors and improve cancer therapy. Probiotics, prebiotics, and vaginal microbiota transplants show potential.
Probiotics appear to have beneficial effects on human endometrial epithelial cells (HEEC) according to a few studies. One particular strain of Lacticaseibacillus rhamnosus:
- Reduced pH (increased pathogen-inhospitable acid).
- Produced organic acids such as lactate, which promotes the reduction of pathogenic bacteria.
- Improved the proinflammatory profile in HEEC cells colonized by pathogens.
And because bacterial vaginosis is linked to endometrial microbial colonization, probiotics that protect against vaginal pathogens may also be beneficial.
Shown to have prebiotic activity, the milk protein lactoferrin was able to modify the endometrial microbiome, increasing Lactobacillus levels in the endometria of non-Lactobacillus dominant patients after three months of use.
The use of probiotics and prebiotics show the potential to provide greater benefits than the use of antibiotics alone, which produces short-term results but which aggravates dysbiosis and promotes resistance over the long term.
Vaginal microbiota transplant
Finally, vaginal microbiota transplants (the transfer of cervicovaginal fluid from a healthy donor to a patient to restore their microenvironment) could be an effective tool for managing endometrial dysbiosis, as uterine colonization by microorganisms through vaginal-cervical ascension has been described.
The endometrial microbiome is implicated in various processes such as inflammation, estrogen metabolism, carcinogenesis, and antitumor treatments. Modulating the endometrial microbiome in combination with traditional endometrial cancer treatments may provide an alternative method to achieve better results.
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