Editorial: Community series in the immunological role of the maternal microbiome in pregnancy, Volume II

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Alterations in endometrial microbial composition have been associated with recurrent implantation failure (RIF) following embryo transfer and with spontaneous miscarriage. A recurrent observation is the depletion of Lactobacillus species accompanied by an increased abundance of facultative and obligate anaerobes. These microbial shifts are thought to disrupt embryo-endometrium signaling and promote a pro-inflammatory or immunologically dysregulated state, ultimately compromising implantation and early placental development (Gao H, Lu N, Chen Y, et al. Endometrial microbiome during early pregnancy among women with and without chronic endometritis: a pilot study. Front Cell Infect Microbiol. 2025;15:1615182. Published 2025Aug 13. doi:10.3389/fcimb.2025.1615182).Maternal factors, including obesity, further shape this microbial landscape. In assisted reproduction, women with higher body mass index exhibit distinct uterine microbiota profiles-characterized by reduced Lactobacillus and increased pathogenic taxa-paralleling lower implantation and pregnancy rates. These findings reinforce the view that metabolic and microbial pathways are closely intertwined (Yan Y, Li Y, Wu L, Zhang Y, Guo H, Ji Y. Correlation between uterine microbiota and pregnancy outcomes of embryo transfer in overweight and obese women. Front Cell Infect Microbiol. 2025;15:1515563. Published 2025Feb 3. doi:10.3389/fcimb.2025.1515563). This perspective extends across pregnancy. A stable, Lactobacillus-dominated vaginal microbiota is consistently associated with term delivery, whereas increased diversity and depletion of protective species are linked to preterm birth. Recent studies suggest that this risk is not only microbial but also metabolic: specific cervicovaginal metabolite profiles, alongside microbial shifts, precede preterm delivery, pointing toward a functional, rather than purely compositional, disruption (Wang L, Zhang J, Zhang M, et al. Insights into the alteration of vaginal microbiota and metabolites in pregnant woman with preterm delivery: prospective cohort study. Front Cell Infect Microbiol. 2025;15:1580801. Published 2025Sep 18. doi:10.3389/fcimb.2025.1580801).What emerges from this body of work is a shift from viewing the microbiota as a passive marker to considering it an active participant in reproductive biology. This shift carries clinical implications, although translation remains at an early stage. Microbiota profiling and integrated metabolomic approaches hold promise for identifying women at risk of implantation failure, miscarriage, preterm birth, and pregnancy complications. At the same time, interventions aimed at modulating the microbiota-through diet, probiotics, or more targeted strategies-are being explored, albeit without definitive evidence for routine use.In this evolving landscape, the critical question is how the microbiota's complexity can be harnessed to inform next-generation diagnostics and therapeutics. Translation into clinical practice demands caution. The field remains constrained by technical variability, low microbial biomass, susceptibility to contamination, and the enduring challenge of distinguishing causation from correlation. Rigorous standardization, longitudinal designs, and mechanistic studies will be essential to bridge this gap.The question is no longer whether the maternal microbiota matters, but how its complexity can be translated into clinically meaningful advances.

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