Postmenopause as a key factor in the composition of the Endometrial Cancer Microbiome (ECbiome)

Abstract

Incidence rates for endometrial cancer (EC) are rising, particularly in postmenopausal and obese women. Previously, we showed that the uterine and vaginal microbiome distinguishes patients with EC from those without. Here, we sought to examine the impact of patient factors (such as menopause status, body mass index, and vaginal pH) in the microbiome in the absence of EC and how these might contribute to the microbiome signature in EC. We find that each factor independently alters the microbiome and identified postmenopausal status as the main driver of a polymicrobial network associated with EC (ECbiome). We identified Porphyromas somerae presence as the most predictive microbial marker of EC and we confirm this using targeted qPCR, which could be of use in detecting EC in high-risk, asymptomatic women. Given the established pathogenic behavior of P. somerae and accompanying network in tissue infections and ulcers, future investigation into their role in EC is warranted.

New Opportunities for Endometrial Health by Modifying Uterine Microbial Composition: Present or Future?

“…Several studies demonstrated that asymptomatic women harbour commensal microbial communities in their uterus [8,11,16,22,102], and that the uterine microbiome seems to be altered in women who suffer gynaecological pathologies such CE [14][15][16], endometriosis [17,19,20], dysfunctional endometrial bleeding [22], endometrial polyps [16], endometrial cancer or hyperplasia [16,[23][24][25], and infertility [4,8,11,13] (Table 1). All these studies support the evidence that the uterine microbial composition is clinically relevant and requires further investigation.…”

“…The uterine microbiome of 'healthy' women was mostly investigated as a control group in studies of infertile women or those with a gynaecological pathology [7,8,11,[13][14][15][16][17][18][19][22][23][24] (Table 1). Nevertheless, these data suggest that commensal microorganisms can inhabit the upper reproductive tract of healthy women.…”

“…Prevailing hypotheses for endometrial cancer aetiology are focused on obesity and hormones, and do not consider the potential role of endometrial microbiota [24]. However, studies in other fields, such as cervical cancer, prostate cancer and gastrointestinal tumours, demonstrated that microorganisms play important roles in cancer causation and development [31,[115][116][117][118].…”

“…The authors suggested that the presence of Atopobium vaginae and Porphyromonas somerae is associated with endometrial cancer [23]. Recently, the same group investigated endometrial cancer risks and they confirmed Porphyromas somerae presence as the most predictive microbial marker of endometrial cancer [24]. Meanwhile, another group studied women undergoing hysterectomy for endometrial tumours and detected Acinetobacter, Pseudomonas, Cloacibacterium, Comamonadaceae, and Escherichia as predominant taxa in the diseased endometrium [25].…”

“…The initial studies of endometrial microbiome suggest its association with reproductive outcomes in assisted reproduction [4][5][6][7][8][9][10][11][12][13] and with different gynaecological pathologies such as chronic endometritis (CE) [14][15][16], endometriosis [13,[17][18][19][20][21], dysfunctional endometrial bleeding [22], endometrial polyps [16], and endometrial cancer or hyperplasia [23][24][25]. Nevertheless, causality has been difficult to prove because the reproductive tract represents a polymicrobial niche [26], and it is not clear whether dysbiosis within the uterus is a cause or a consequence of a pathology.…”