Endometrial microbiota in infertile women with and without chronic endometritis as diagnosed using a quantitative and reference range-based method

Abstract

Objective: To systematically compare the endometrial microbiota in infertile women with and without chronic endometritis (CE), as diagnosed by a quantitative and reference range-based method. Design: Case-control observational study. Setting: University-affiliated hospital. Patient(s): One hundred and thirty infertile women. Intervention(s): Endometrial biopsy and fluid (uterine lavage, UL) collected precisely 7 days after LH surge, with plasma cell density (PCD) determined based on Syndecan-1 (CD138)-positive cells in the entire biopsy section and culture-independent massively parallel sequencing of the 16S ribosomal RNA gene performed on both the CE and non-CE endometrial fluid samples. Main Outcome Measure(s): Relative abundance of bacterial taxa. Result(s): Chronic endometritis was diagnosed if the PCD was above the 95th percentile (>5.15 cells per 10 mm 2 ) of the reference range in fertile control subjects. With this stringent diagnostic criterion, 12 women (9%) were diagnosed with CE. Sequencing was successfully performed on all endometrial samples obtained by UL) (CE, n ¼ 12; non-CE, n ¼ 118). The median relative abundance of Lactobacillus was 1.89% and 80.7% in the CE and non-CE microbiotas, respectively. Lactobacillus crispatus was less abundant in the CE microbiota (fold-change, range: 2.10-2.30). Eighteen non-Lactobacillus taxa including Dialister, Bifidobacterium, Prevotella, Gardnerella, and Anaerococcus were more abundant in the CE microbiota (fold-change, 2.10-18.9). Of these, Anaerococcus and Gardnerella were negatively correlated in relative abundance with Lactobacillus (SparCC correlation magnitude, range: 0.142-0.177). Conclusion(s): Chronic endometritis was associated with a statistically significantly higher abundance of 18 bacterial taxa in the endometrial cavity.

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.…”

“…Alteromonas [16], Anaerococcus [15], Atopobium [15], Bifidobacterium [14][15][16], Dialister [15], Gardnerella [14][15][16], Lactobacillus [14,16], Magasphaera [14], Parvimonas [14], Prevotella [14,15], Propionibacterium [14], Streptococcus [14,16], Veillonella [14] Endometrial polyps Alteromonas [16], Bifidobacterium [16], Euryarchaeota (Archaea) [16], Gardnerella [16], Lactobacillus [16], Streptococcus [16] Dysfunctional menstrual bleeding Gardnerella [22], Lactobacillus [22], Prevotella [22], Sneathia [22], Veilonella [22] Endometrial cancer…”

“…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.…”

“…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.…”

Immunological Role of the Maternal Uterine Microbiome in Pregnancy: Pregnancies Pathologies and Alterated Microbiota

“…However, given that only 16S methodology was used it is unclear whether certain species or subspecies of Lactobacillus may be capable of conferring this benefit. A recent study on the endometrial microbiota and chronic endometritis reported that Lactobacillus crispatus was less abundant in patients with CE suggesting that there may be certain Lactobacillus spp that is protective (27). More comprehensive whole genome shotgun sequencing (WGS) may help answer this question.…”