The Role of Microbiota in the Immunopathogenesis of Endometrial Cancer

Abstract

The female reproductive tract hosts a specific microbiome, which plays a crucial role in sustaining equilibrium and good health. In the majority of reproductive women, the microbiota (all bacteria, viruses, fungi, and other single-celled organisms within the human body) of the vaginal and cervical microenvironment are dominated by Lactobacillus species, which benefit the host through symbiotic relationships, in comparison to the uterus, fallopian tubes, and ovaries, which may contain a low-biomass microbiome with a diverse mixture of microorganisms. Although disruption to the balance of the microbiota develops, the altered immune and metabolic signaling may cause an impact on diseases such as cancer. These pathophysiological modifications in the gut–uterus axis may spark gynecological cancers. New information displays that gynecological and gastrointestinal tract dysbiosis (disruption of the microbiota homeostasis) can play an active role in the advancement and metastasis of gynecological neoplasms, such as cervical, endometrial, and ovarian cancers. Understanding the relationship between microbiota and endometrial cancer is critical for prognosis, diagnosis, prevention, and the development of innovative treatments. Identifying a specific microbiome may become an effective method for characterization of the specific microbiota involved in endometrial carcinogenesis. The aim of this study was to summarize the current state of knowledge that describes the correlation of microbiota with endometrial cancer with regard to the formation of immunological pathologies.

Endometrial microbiota in women with and without adenomyosis: A pilot study

“…However, several studies have shown that the endometrium is colonized by bacterial strains that differ from the vaginal microbiota (Moreno et al, 2016;Chen et al, 2017). Dysbiosis of the endometrial microbiota is likely to lead to endometrial cancer (Walther-António et al, 2016;Sobstyl et al, 2022), polyps (Fang et al, 2016), endometriosis (Akiyama et al, 2019;Wessels et al, 2021), endometritis (Moreno et al, 2018;Hernandes et al, 2020), and recurrent pregnancy loss (Łaniewski et al, 2020). A recent study confirmed that Porphyromonas somerae represents a suitable biomarker for endometrial cancer (Walsh et al, 2019).…”

Gut and genital tract microbiomes: Dysbiosis and link to gynecological disorders

“…A low percentage of Lactobacillus in the female vaginal sample is less likely to have a successful embryo implantation, with an interplay between the uterine microenvironment and the host's immune system (Moreno et al, 2022). This involves increased proinflammatory cytokine production in endometrial cells, including interleukin (IL)-1a, IL-1b, IL-17a, and tumor necrosis factor (TNF)-a, due to the estrogen-dependent nature of endometrial cell cytokine production (Sobstyl et al, 2022). However, other groups reported that Proteobacteria, Firmicutes, and Bacteroidetes were prevalent in endometrial samples, while Lactobacillus spp.…”

Vaginal microbes alter epithelial transcriptomic and epigenomic modifications providing insight into the molecular mechanisms for susceptibility to adverse reproductive outcomes

“…Gene-disease enrichment analysis of these transcription factors demonstrated a marked enrichment of multiple pathways related to neoplasms, endometriosis and infertility, all pathologies potentially associated with Lactobacillus-dominated microbiota (Fig. 7G) 36,37 . To determine if this enrichment was speci c, we generated random lists of transcription factors from the same motif database and demonstrated only an overlapping enrichment in unrelated craniofacial anomalies, suggesting our ndings are indeed speci c (Supplemental Fig.…”