Dysbiosis of the endometrial microbiota and its association with inflammatory cytokines in endometrial cancer

Abstract

The underlying molecular mechanisms involved in the pathogenesis of endometrial cancer (EC) are still not well understood. Our goal was to investigate the composition of the endometrial microbiota and the association with inflammatory cytokines in EC. Endometrial microbiota profiles of women with EC (n = 25) and benign uterine lesions (BUL, n = 25) were assessed by 16S ribosomal RNA gene amplicon sequencing. The expression levels of interleukin‐6 (IL‐6), interleukin‐8 (IL‐8), and interleukin‐17 (IL‐17) mRNA and protein in the endometrial tissues of the two groups were determined by real‐time quantitative polymerase chain reaction and Western blot, respectively. There were significant differences in alpha diversity based on the observed operational taxonomic units (P = .002), Pielou evenness (P = .001), and Shannon index (P < .001) between EC and BUL groups. Significant differences were also found in Bray‐Curtis (P = .001) and unweighted UniFrac (P = .001) beta diversity measures between the two groups. At the genus level, Micrococcus was more abundant in the EC group. Pseudoramibacter_Eubacterium, Rhodobacter, Vogesella, Bilophila, Rheinheimera, and Megamonas were enriched in the BUL group. There were no differences in IL‐8 and IL‐17 protein levels between the two groups, except IL‐6 protein levels. However, the mRNA expression levels of IL‐6, IL‐8, and IL‐17 were significantly different. Moreover, the relative abundances of Micrococcus was positively correlated with IL‐6, and IL‐17 mRNA levels. In conclusion, our results suggested that dysbiosis of endometrial microbiota and the inflammatory cytokines were associated with Micrococcus in EC patients, which might be useful for exploration of the mechanism between the endometrial microbiota and inflammatory responses in future studies.

A Review of the Clinical Characteristics and Novel Molecular Subtypes of Endometrioid Ovarian Cancer

“…Where there is persistent dysbiosis of the microbial environment, altered immune and metabolic signaling can result in oxidative stress and the recruitment of immune cells which release reactive oxygen species (ROS), which may result in inflammation–driven carcinogenesis ( 40 , 41 ). At present, the study of endometrial microbiota has reported that EC is associated with particular microorganisms ( 42 ). Similarly, related studies have also indicated that many microorganisms are involved in the development of EOC, such as Proteobacteria and Firmicutes ( 43 ).…”

Gut and Endometrial Microbiome Dysbiosis: A New Emergent Risk Factor for Endometrial Cancer

“…Winters et al also sequenced endometrial samples from 25 women who underwent total hysterectomy for fibroids or endometrial hyperplasia, and found that the most abundant genera in their endometria were Acinetobacter , Pseudomonas , Comamonadaceae , and Cloacibacterium [ 30 ]. Finally, in a more recent study, Lu et al also suggested that Lactobacillus is not the predominant genus in the endometrium, observing a greater abundance of Rhodococcus , Phyllobacterium , Sphingomonas , Bacteroides , and Bifidobacterium [ 31 ] ( Table 1 ).…”

“…This decrease in the diversity of microorganisms led to the overgrowth of the few remaining species and a decrease in resilience. Furthermore, in this study, Pseudomoramibacter_Eubacterium , Rhodobacter , Vogesella , Bilophila , Rheinheimera , and Megamonas were enriched in patients with benign uterine lesions, while Micrococcus was associated with an inflammatory profile in endometrial cancer [ 31 ].…”

Microbiota and epigenetics: promising therapeutic approaches?

“…Similarly, the metabolization of alcohol by oral microbiota to produce acetaldehyde interferes with DNA repair and enhances chromosomal damage. In addition to the role of gut and breast microbiome in cancer pathogenesis, disturbances in bladder, ovarian, vaginal, uterine, male genital tract, and pulmonary microbiome can also initiate local carcinogenicity(El-Sayed et al 2021a ; Haque et al 2021 ; Lu et al 2020 ; Perrone et al 2021 ; Thomas et al 2021 ; Tuominen et al 2021 ), and in addition to the role of some microbiota in cancer development, many members of our virome are also incriminated in triggering various types of cancers(Haque et al 2021 ). It is of high interest that the microbiota not only induce cancer but they can also interact with cancer therapeutic protocols.…”