Re‐assessing microbiomes in the low‐biomass reproductive niche

Abstract

The female reproductive tract represents a continuum between the vagina and the upper genital tract. New evidence from cultivation‐independent studies suggests that the female upper genital tract is not sterile; however, the significance of this for reproductive health and disease remains to be elucidated fully. Further, diagnosis and treatment of infectious reproductive tract pathologies using cultivation‐independent technologies represents a largely unchartered area of modern medical science. The challenge now is to design well‐controlled experiments to account for the ease of contamination known to confound molecular‐based studies of low‐biomass niches, including the uterus and placenta. This will support robust assessment of the potential function of microorganisms, microbial metabolites, and cell‐free bacterial DNA on reproductive function in health and disease. Tweetable abstract Molecular microbial studies of low‐biomass niches require stringent experimental controls to reveal causal relations in reproductive health and disease.

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

“…In fact, there is an active debate ongoing whether uterus harbours a unique microbiota or not [25]. If the microbiome is certainly present in the uterine environment in the absence of pathologic infection, current data support that it is of low abundance [26,168], and several technical challenges in studies of low-biomass samples exist and make difficult to distinguish microorganisms that are truly present in small quantities from those arisen from contamination [26,91,92]. Thus, the appropriate uterine microenvironment for non-pathological conditions has yet to be established and applying methods for targeted modification of microbial communities is premature.…”

“…Regardless of the different intrinsic factors, probably one of the most important challenges that arises in modulating the endometrial microbiome is the fact that it is a low microbial biomass niche [26,165]. It is clear that analyses of low-biomass microbial sites are sensitive to contamination (especially from lower genital tract) and data misinterpretation.…”

“…It is clear that analyses of low-biomass microbial sites are sensitive to contamination (especially from lower genital tract) and data misinterpretation. Thus, researchers face hurdles when describing the baseline microbial communities in endometrium and require well-designed and well-controlled experiments in order to avoid and adjust for the risk of contamination [26,91]. This makes especially necessary to set up standardised detection and description methods for analysing the uterine microbial composition, as well as strategies to re-establish/maintain these microbial populations.…”

“…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.…”

“…Sample processing: amplicon sequencing has shown to cause great variance [75,90]. Low-biomass: high risk of misinterpretation of the results [26,91,92]. Analyses and interpretation: statistical analyses and interpretation can induce bias [84,90,93].…”