Study Question: Does the gut microbiota play a role in changing the local immune response to an adverse vaginal microbiota?

Summary Answer: In women with an adverse vaginal microbiota, a healthy gut microbiota appears to dampen cervico-vaginal inflammation and may offer protection against euploid miscarriage.

What Is Known Already:

An adverse vaginal microbiota has been linked to heightened inflammation and poor reproductive outcomes, such as euploid miscarriage. However, not all women with such microbiota experience pregnancy loss, suggesting a modulatory role of other factors like gut microbiota.

Study Design:

• Prospective observational cohort study conducted at Queen Charlotte’s and Chelsea Hospital, London (July 2017–February 2019).
• Sample: 47 miscarriage cases (29 euploid, 18 aneuploid) and 49 viable pregnancies.
• Vaginal and rectal microbiota were analysed using 16S rRNA metataxonomics. Cytokine levels (IL-2, IL-4, IL-6, IL-8, TNF-α, IFN-γ, IL-1β, IL-18, IL-10) were measured in cervicovaginal fluid. Microbiota characteristics and cytokine profiles were correlated across different pregnancy outcomes.

Results:

1. No difference in rectal microbiota richness/diversity across pregnancy outcomes.
2. In women with adverse vaginal microbiota, the Firmicutes/Bacteroidetes (F/B) ratio was significantly higher in euploid miscarriage vs aneuploid miscarriage (P=0.02).
3. Euploid miscarriage was enriched with Finegoldia magna, Prevotella bivia, Dialister invisus, and Peptoniphilus gorbachii.
4. Aneuploid miscarriage had higher abundance of Clostridium XIVa and Bacteroidetes.
5. A low F/B ratio (healthy gut) was associated with higher anti-inflammatory cytokines (IL-4, IL-10) in patients with an adverse vaginal microbiota (P=0.01 and P=0.04, respectively).
6. Rectal dysbiosis had no effect on cytokine levels in those with a healthy vaginal microbiota.

Limitations: As a preliminary observational study, findings are exploratory. Further research with longitudinal data, stool cultures, and lifestyle profiling is needed to better understand gut–vaginal–immune interactions.

Wider Implications of the Findings: Evidence suggests crosstalk between vaginal and gut microbiota may influence immune responses in pregnancy. This supports the potential role of dietary interventions and live bio-therapeutics in improving reproductive outcomes.

ESHRE 2025, June 29 - July 2, Paris