Taxonomical and Functional Assessment of the Endometrial Microbiota in A Context of Recurrent Reproductive Failure: A Case Report

Abstract

Investigation of the microbial community in the female reproductive tract has revealed that the replacement of a community dominated by Lactobacillus with pathogenic bacteria may be associated with implantation failure or early spontaneous abortion in patients undergoing assisted reproductive technology (ART) treatment. Herein we describe taxonomically and functionally the endometrial microbiome of an infertile patient with repeated reproductive failures (involving an ectopic pregnancy and two clinical miscarriages). The microbiological follow-up is presented over 18-month in which the microbiota was evaluated in six endometrial fluid samples. The microbial profile of 16S rRNA gene sequencing showed a persistent infection with Gardnerella and other bacterial taxa such as Atopobium and Bifidobacterium. In addition, taxonomic and functional analysis by whole metagenome sequencing in the endometrial fluid sample collected before one clinical miscarriage suggested the presence of multiple Gardnerella vaginalis clades with a greater abundance of clade 4, usually associated with metronidazole resistance. These results revealed a persistent G. vaginalis endometrial colonization presenting genetic features consistent with antimicrobial resistance, biofilm formation, and other virulence factors, which could be related to the reproductive failure observed.

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

“…(2) the integrity of the epithelial barrier could be impaired; and (3) the microbial-secreted metabolites and the inflammation triggered by TLR activation could lead to suppression and/or overgrowth of specific bacteria [30]. The potential molecular functions of the endometrial microbes were linked to cell metabolism, motility, genetic information, immune system, and signalling processes in the NGS studies [5,20]. Regardless of all these hypotheses, future studies are needed to identify the basal uterine microbiota, its diversity and its functions and interactions with the endometrium.…”

“…Atopobium [6,[8][9][10], Bacteroides [12], Betaproteobacteria [12], Bifidobacterium [5,[8][9][10][11]13,104], Burkholderia [7], Chitinophagaceae [12], Corynebacterium [104], Escherichia/Shigella [10,12], Flavobacterium [4], Gardnerella [5][6][7][8][9][10][11]13], Lactobacillus [4][5][6][7][8][9][10][11]13,104], Megasphaera [9,10], Pelomonas [12], Prevotella [8][9][10][11]13], Pseudoalteromonas [5], Rhodanobacter [5], Sneathia [8,9], Staphylococcus [8]…”

“…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.…”

The Reproductive Journey in the Genomic Era: From Preconception to Childhood

“…Aside from the assessment of the embryo´s mutational/chromosomal status, additional genetic tests assessing fertility, based on high-throughput techniques such as NGS, are beyond the scope of an ordinary clinical practice to increase the reproductive chances of a couple, i.e., endometrial receptivity analysis and more recently, endometrial microbiome test [ 14 , 15 ].…”

“…Prenatal screening is the risk estimation of fetal aneuploidies based on high-resolution ultrasound scans, in order to assess ultrasonographic markers including nuchal translucency, combined with biochemical determinations in maternal blood samples of free beta-subunit of human chorionic gonadotropin (fβ-hCG) and pregnancy-associated plasma protein-A (PAPP-A) in the first trimester, and the alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (βhCG) in the second trimester [ 15 ]. If this risk of congenital defect is high, invasive procedures such as chorionic villus sampling (CVS) or amniocentesis are recommended [ 16 ].…”