Potential biomarkers of infertility associated with microbiome imbalances Original paper

What was studied?

This study explored the relationship between microbiome imbalances in the vaginal and rectal environments and infertility in women experiencing repeated in vitro fertilization (IVF) failures. Researchers specifically investigated the expression levels of microRNAs (miRNAs), particularly miR-21-5p and miR-155-5p, alongside microbiota composition differences between infertile and fertile women. The study aimed to determine whether these microbiome alterations and miRNA levels could serve as potential biomarkers for unexplained infertility.

Who was studied?

The study included 287 women diagnosed with unexplained infertility who had experienced multiple IVF failures, along with 20 fertile women as controls. The infertile group was characterized by an average age of 40, had a history of at least two unsuccessful IVF attempts, and exhibited normal ovarian and tubal anatomy. The fertile group comprised women who had conceived naturally, were aged between 29 and 38, and had no infertility or autoimmune conditions. Vaginal and rectal swabs were collected for microbiota sequencing and miRNA expression analysis. Blood and saliva samples were also analyzed for immunometabolic markers.

What were the most important findings?

Significant microbiota differences between infertile and fertile groups emerged from this study. Infertile women showed reduced microbial diversity in their rectal microbiome, characterized by an increased ratio of Firmicutes to Bacteroidetes. This imbalance correlated with markers indicative of gut barrier dysfunction. In vaginal samples, infertile women demonstrated a unique microbial pattern, primarily an increased ratio of Lactobacillus brevis to Lactobacillus iners, which contrasts with the typical Lactobacillus dominance associated with healthy reproductive outcomes.

Two miRNAs—miR-21-5p and miR-155-5p—were notably elevated in both vaginal and rectal samples from infertile patients. MiR-21-5p was associated with increased gut permeability, fungal overgrowth, and reduced microbial diversity, whereas miR-155-5p correlated with inflammation and bacterial dysbiosis. Receiver operating characteristic (ROC) analyses confirmed that elevated levels of these miRNAs could reliably distinguish infertile women from fertile women, demonstrating their potential as effective biomarkers for infertility linked to microbiome imbalances.

What are the greatest implications of this study?

The greatest clinical implication is the potential use of microbiome profiling and miRNA expression levels as diagnostic and prognostic tools in managing infertility, especially in cases of unexplained repeated IVF failures. Identifying microbiome dysbiosis and associated inflammatory markers through miRNAs may allow clinicians to personalize treatment plans, potentially involving microbiota-modifying therapies such as probiotics or targeted nutritional interventions. This approach could significantly enhance fertility treatment outcomes by restoring microbiome balance and reducing inflammatory states that adversely affect fertility. Moreover, understanding the link between gut and reproductive tract microbiota suggests that comprehensive evaluation and management of microbiome health should be integral to infertility assessments.