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PloS one2025; 20(4); e0321389; doi: 10.1371/journal.pone.0321389

Metagenomic and proteomic analyses reveal similar reproductive microbial profiles and shared functional pathways in uterine immune regulation in mares and jennies.

Abstract: This study aims to unveil potential differences in the vaginal and uterine microbiomes in mares and jennies, and to identify possible mechanisms involved in uterine immune homeostasis. The microbiota was characterized using 16S rRNA sequencing, and the uterine proteome was analyzed using UHPLC/MS/MS in 18 samples from healthy mares and 14 from jennies. While taxonomic analysis revealed high interspecies similarities, β-diversity analysis showed distinct clustering, with only two vaginal taxa and five uterine taxa differing between species. Despite compositional differences, PICRUSt analysis suggested minimal variations in predicted functional pathways across species. Comparing vaginal and uterine microbiota within the same species revealed overlapping bacterial taxa, but significant differences in α- and β-diversity and functional pathways. The uterine microbiota of both species was dominated by Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria, with abundant taxa like Streptococcus, Pseudomonas, Bacillus, Corynebacterium, and Staphylococcus, many of which are frequently associated with endometritis. The presence of Lactobacillus in the equine reproductive tract was minimal or non-existent. KEGG functional pathway analysis predicted that uterine microbiota of both species utilize metabolic pathways with potential immunomodulatory effects. Proteomic enrichment analysis showed that numerous overexpressed uterine proteins in both species are linked to adaptive and innate immune regulation and defense mechanisms against symbionts. Gene enrichment analysis identified several enriched Gene Ontology terms, including response to bacterial stimuli, humoral immune regulation, and TGF-beta receptor signaling, underscoring microbial-host interactions. The uterine microbiota may play a vital role in maintaining immune balance. Further research is required to confirm its interaction with the uterine immune system and clarify the mechanisms involved.
Copyright: © 2025 da Silva-Álvarez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Publication Date: 2025-04-16 PubMed ID: 40238748PubMed Central: PMC12002498DOI: 10.1371/journal.pone.0321389Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study explores the potential differences and similarities in the vaginal and uterine microbiomes of mares and jennies, with a focus on the possible mechanisms that help maintain uterine immune balance.

Methodology

  • The research incorporated metagenomic and proteomic analyses of 18 samples from healthy mares and 14 from jennies.
  • Microbiota was characterized using 16S rRNA sequencing, a technique that enables the identification and study of microorganisms within the tested samples.
  • UHPLC/MS/MS technique (ultra high-performance liquid chromatography coupled with tandem mass spectrometry) was employed to analyze the uterine proteome or the set of expressed proteins in a cell, tissue, or organism.

Findings

  • The taxonomic analysis showed high interspecies microbiota similarities between mares and jennies.
  • A beta diversity analysis indicated a distinct clustering in both species, signifying different species abundance and distribution.
  • Although there were compositional differences, the PICRUSt analysis indicated minimal variations in the predicted functional pathways across both species.
  • When comparing the vaginal and uterine microbiota within the same species, there were overlapping bacterial taxa but noticeable differences in alpha and beta diversity and functional pathways.
  • The uterine microbiota of both species was dominated by Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria. Common taxa, such as Streptococcus, Pseudomonas, Bacillus, Corynebacterium, and Staphylococcus, were abundant.

Implications of the Study

  • Many of the microbes are frequently found in conditions such as endometritis, suggesting a link between certain bacteria and uterine health.
  • The researchers found surprisingly little or non-existent traces of Lactobacillus, a type of bacteria known to be beneficial for human reproductive health, in the equine reproductive tract.
  • The data interpreted from the KEGG (Kyoto Encyclopedia of Genes and Genomes) functional pathway analysis suggested that the uterine microbiota of both species utilize metabolic pathways that may have immunomodulatory effects, implicating that the uterine microbiota may play a role in the immune regulation of the uterus.
  • Proteomic enrichment analysis found that several overexpressed uterine proteins in both species are linked to adaptive and innate immune regulation, suggesting microbial-symbiont defensive interactions.
  • The gene enrichment analysis identified several enriched Gene Ontology terms, emphasizing a mutual interaction between the host and microbes.
  • However, despite these promising results, further research is needed to confirm the interplay between uterine microbiota and the immune system and clarify the mechanisms involved in maintaining immune balance within the uterus.

Cite This Article

APA
da Silva-Álvarez E, Gómez-Arrones V, Correa-Fiz F, Martín-Cano FE, Gaitskell-Phillips G, Carrasco JJ, Rey J, Aparicio IM, Peña FJ, Alonso JM, Ortega-Ferrusola C. (2025). Metagenomic and proteomic analyses reveal similar reproductive microbial profiles and shared functional pathways in uterine immune regulation in mares and jennies. PLoS One, 20(4), e0321389. https://doi.org/10.1371/journal.pone.0321389

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 20
Issue: 4
Pages: e0321389

Researcher Affiliations

da Silva-Álvarez, Eva
  • Department of Animal Medicine, Laboratory of Equine Reproduction and Equine Spermatology, Faculty of Veterinary Medicine, University of Extremadura, Cáceres, Spain.
Gómez-Arrones, Vanessa
  • Centro de Selección y Reproducción animal de Extremadura. Junta de Extremadura, Badajoz, Spain.
Correa-Fiz, Florencia
  • Centre de Recerca en Sanitat Animal (CReSA), Unitat Mixta d'Investigació IRTA-UAB en Sanitat Animal, Campus de la Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.
  • IRTA, Programa de Sanitat Animal, Centre de Recerca en Sanitat Animal (CReSA), Campus de la Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.
  • WOAH Collaborating Centre for the Research and Control of Emerging and Re-Emerging Swine Diseases in Europe (IRTA-CReSA), Barcelona, Spain.
Martín-Cano, Francisco Eduardo
  • Department of Animal Medicine, Laboratory of Equine Reproduction and Equine Spermatology, Faculty of Veterinary Medicine, University of Extremadura, Cáceres, Spain.
Gaitskell-Phillips, Gemma
  • Department of Animal Medicine, Laboratory of Equine Reproduction and Equine Spermatology, Faculty of Veterinary Medicine, University of Extremadura, Cáceres, Spain.
Carrasco, Juan Jesús
  • Centro de Selección y Reproducción animal de Extremadura. Junta de Extremadura, Badajoz, Spain.
Rey, Joaquín
  • Department of Animal Health, Unit of Infectious Diseases, University of Extremadura, Caceres, Spain.
Aparicio, Inés María
  • Department of Anatomy, Cell Biology and Zoology, Faculty of Nursery and Occupational Therapy, University of Extremadura, Caceres, Spain.
Peña, Fernando Juan
  • Department of Animal Medicine, Laboratory of Equine Reproduction and Equine Spermatology, Faculty of Veterinary Medicine, University of Extremadura, Cáceres, Spain.
Alonso, Juan Manuel
  • Department of Animal Health, Unit of Infectious Diseases, University of Extremadura, Caceres, Spain.
Ortega-Ferrusola, Cristina
  • Department of Animal Medicine, Laboratory of Equine Reproduction and Equine Spermatology, Faculty of Veterinary Medicine, University of Extremadura, Cáceres, Spain.

MeSH Terms

  • Animals
  • Female
  • Horses / microbiology
  • Horses / immunology
  • Uterus / microbiology
  • Uterus / immunology
  • Uterus / metabolism
  • Proteomics / methods
  • Microbiota / genetics
  • RNA, Ribosomal, 16S / genetics
  • Metagenomics
  • Vagina / microbiology
  • Vagina / immunology
  • Bacteria / genetics
  • Bacteria / classification
  • Proteome

Conflict of Interest Statement

The authors have declared that no competing interests exist.

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