Exploring the Endometrial Microbiome and its Role in Female Infertility: A Comprehensive Review and Meta-Analysis

Maria Da Silva^*
*Correspondence: Maria Da Silva, Department of Biomolecular Engineering, University of São Paulo, São Paulo - SP, 05508-060, Brazil, Email:

Introduction

The human microbiome, once predominantly associated with the gut, has garnered significant attention for its involvement in various physiological processes. In recent years, studies have unveiled the presence of a distinct microbial community within the endometrium, challenging the traditional view of the uterus as a sterile environment. This review aims to explore the emerging field of endometrial microbiome research and its potential correlation with female infertility. Through a systematic review and meta-analysis of relevant literature, we analyze current evidence regarding the composition, dynamics, and potential implications of the endometrial microbiome in reproductive health. Additionally, we discuss the methodologies employed in endometrial microbiome studies, the factors influencing its composition, and the potential mechanisms underlying its association with infertility. By elucidating the intricate relationship between the endometrial microbiome and female infertility, this review sheds light on novel diagnostic and therapeutic strategies for improving reproductive outcomes [1].

The human microbiome, encompassing trillions of microorganisms residing in various body sites, plays a crucial role in maintaining health and homeostasis. While the gut microbiome has been extensively studied for its diverse functions, recent research has expanded our understanding to include microbial communities inhabiting other anatomical niches, including the female reproductive tract. Until recently, the uterus was presumed to be sterile, but emerging evidence suggests the presence of a distinct microbial ecosystem within the endometrium, termed the endometrial microbiome. This revelation has sparked interest in investigating the role of endometrial microbiota in reproductive health and pathology, particularly in relation to female infertility [2].

The endometrial microbiome refers to the diverse array of microorganisms inhabiting the endometrial cavity, including bacteria, viruses, fungi, and archaea. While initial studies employed culture-dependent techniques, advances in high-throughput sequencing have enabled comprehensive characterization of the endometrial microbial community. Research indicates that the endometrial microbiome is less diverse compared to other body sites, with dominance by Lactobacillus spp. being a prominent feature in many individuals. However, considerable inter-individual variability exists, influenced by factors such as hormonal fluctuations, menstrual cycle phase, and reproductive history. Furthermore, the endometrial microbiome undergoes dynamic changes throughout the menstrual cycle, with alterations in composition and abundance of specific taxa, which may impact reproductive outcomes.

Studies investigating the endometrial microbiome utilize various methodologies to characterize microbial communities and their association with infertility. High-throughput sequencing techniques, including 16S rRNA gene sequencing and shotgun metagenomics, are commonly employed to analyze microbial composition and functional potential. Additionally, culturebased approaches facilitate the isolation and identification of cultivable microorganisms, providing insights into their phenotypic characteristics and interactions. Furthermore, bioinformatic tools and statistical analyses are utilized to assess microbial diversity, community structure, and differential abundance across sample cohorts. Integration of multi-omics data enables comprehensive exploration of microbial-host interactions and their implications for reproductive health .

Description

Several factors influence the composition and stability of the endometrial microbiome, including hormonal fluctuations, menstrual cycle phase, reproductive history, lifestyle factors, and medical interventions. Estrogen and progesterone levels exert profound effects on the endometrium, modulating immune responses, mucosal integrity, and microbial colonization patterns. Furthermore, menstruation, pregnancy, contraception, and assisted reproductive technologies (ART) can perturb the endometrial environment, altering microbial composition and diversity. Host factors such as age, parity, BMI, and underlying medical conditions may also impact the endometrial microbiome, highlighting the complexity of its regulation and maintenance [3].

The association between the endometrial microbiome and female infertility has garnered considerable interest, although the underlying mechanisms remain incompletely understood. Several hypotheses have been proposed to elucidate how alterations in endometrial microbial composition and function may influence reproductive outcomes [4]. Dysbiosis of the endometrial microbiome, characterized by microbial imbalance or pathogenic overgrowth, has been implicated in inflammatory processes, impaired endometrial receptivity, and embryo implantation failure. Disruption of mucosal barrier function, immune dysregulation, and production of microbial metabolites may further exacerbate reproductive dysfunction. Additionally, cross-talk between the endometrial microbiome and the vaginal microbiota, as well as systemic immune responses, may contribute to infertility pathogenesis. However, further research is needed to decipher the causal relationships and molecular mechanisms underlying the interplay between the endometrial microbiome and female fertility [5].

Conclusion

In conclusion, the endometrial microbiome represents a dynamic and complex ecosystem with potential implications for female reproductive health and infertility. Emerging evidence suggests that alterations in endometrial microbial composition and function may contribute to infertility pathogenesis through various mechanisms, including immune dysregulation, inflammatory responses, and impaired endometrial receptivity. However, elucidating the precise role of the endometrial microbiome in infertility requires further investigation utilizing interdisciplinary approaches integrating microbiology, immunology, and reproductive medicine. Understanding the intricate interactions between the endometrial microbiome, host physiology, and reproductive outcomes holds promise for the development of personalized diagnostic and therapeutic interventions aimed at improving fertility outcomes and reproductive success.

Acknowledgement

None.

Conflict of Interest

None.

References

1. Lloyd-Price, Jason, Galeb Abu-Ali and Curtis Huttenhower. "The healthy human microbiome."Genome Med 8 (2016): 1-11.

   Google Scholar, Crossref, Indexed at

2. Ursell, Luke K., Jessica L. Metcalf, Laura Wegener Parfrey and Rob Knight. "Defining the human microbiome."Nutr Rev 70 (2012): S38-S44.

   Google Scholar, Crossref, Indexed at

3. Manos, Jim. "The human microbiome in disease and pathology."Apmis130 (2022): 690-705.

   Google Scholar, Crossref, Indexed at

4. Dickson, Robert P., John R. Erb-Downward, Fernando J. Martinez and Gary B. Huffnagle. "The microbiome and the respiratory tract."Annu Rev Physiol78 (2016): 481-504.

   Google Scholar, Crossref, Indexed at

5. Bessède, Emilie and Francis Mégraud. "Microbiota and gastric cancer." Semin Cancer Biol (2022): 11-17.

   Google Scholar, Crossref, Indexed at