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Mapping the entire functionally active endometrial microbiota.

Alberto Sola-Leyva1,2, Eduardo Andrés-León3, Nerea M Molina1,2

  • 1Department of Biochemistry and Molecular Biology, Faculty of Sciences, University of Granada, Granada 18071, Spain.

Human Reproduction (Oxford, England)
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The human endometrium hosts active microorganisms, including bacteria, fungi, viruses, and archaea. Their composition and metabolic functions change throughout the menstrual cycle, impacting endometrial receptivity.

Keywords:
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Area of Science:

  • Microbiology
  • Reproductive Medicine
  • Metagenomics

Background:

  • The presence and activity of microorganisms within the endometrium are not fully understood.
  • Previous studies detected microbial DNA, but the viability and functional activity of these microbes remained unclear.
  • The cyclical changes in endometrial microbial composition and function throughout the menstrual cycle were an open question.

Purpose of the Study:

  • To determine if the human endometrium harbors functionally active microorganisms.
  • To investigate whether the endometrial microbial composition differs between the proliferative and mid-secretory phases of the menstrual cycle.
  • To explore the metabolic functions of the endometrial microbiota and its interaction with the host.

Main Methods:

  • RNA sequencing (RNAseq) was performed on 14 paired endometrial samples from healthy women (7 proliferative, 7 mid-secretory phases).
  • A novel metatranscriptomic approach was used to map active microbial RNA sequences.
  • Bioinformatic tools (Kraken2, Krona, metagenomeSeq, HUMANn2) were employed for taxonomic and functional analysis, with statistical comparisons between phases.

Main Results:

  • The study identified over 5300 active microorganisms, including bacteria, fungi, viruses, and archaea, within the healthy human endometrium.
  • Significant differences in microbial abundance were observed between the mid-secretory and proliferative phases.
  • Evidence suggests host-microbiota crosstalk in the receptive endometrium, particularly involving prostanoid biosynthesis and L-tryptophan metabolism.

Conclusions:

  • The human endometrium hosts a diverse and active microbial community whose composition and function vary cyclically.
  • Microbial dysfunction in the endometrium may impair key metabolic pathways essential for reproductive receptivity.
  • This research introduces a novel pipeline for analyzing active microbes, potentially advancing reproductive medicine research.