A study involving mice and humans suggests that a bacterial supplement could improve female fertility

The press release is reasonably faithful to the content of the study, although its headline — ‘Bacterial supplements could improve female fertility’ — oversimplifies a study that is fundamentally pre-clinical and observational. The word ‘supplements’ may lead patients to self-medicate with commercially available L. gasseri probiotics, something which the authors themselves explicitly advise against in the text of the article but which the headline does not convey with the same caution.

From a methodological perspective, the study is robust and ambitious in its multi-level design: it combines a clinical cohort of 149 infertile women with functional screening of strains, cellular models of D-galactose-induced senescence, murine models of advanced reproductive age and, notably, bidirectional genetic disruption —deletion of the exopolysaccharide (EPS) synthesis gene in the bacterium and silencing of Yap1 in the murine uterus via AAV9—. This strategy reinforces the proposed causal chain: L. gasseri → EPS → modulation of the Hippo-YAP pathway → improvement in endometrial receptivity. Publication in Cell Host & Microbe, a leading journal in the field of host–microorganism interaction, attests to the quality of the work.

However, there are important limitations that should be highlighted. The human cohort is single-centre (Peking University Third Hospital), the endometrial samples are of low biomass—with an inherent risk of contamination despite the decontamination controls applied—and the design is a cross-sectional study with follow-up, rather than an interventional study. Clinical pregnancy rates did not differ significantly between age groups, which the authors acknowledge may reflect a lack of statistical power and the equalising effect of embryo selection in IVF (in vitro fertilisation). In other words, the association between endometrial Lactobacillus abundance and reproductive outcome, whilst consistent in the expected direction, does not reach statistical significance in all comparisons.
The main unresolved confounding factor is hormonal. The composition of the reproductive tract microbiome is closely dependent on oestrogen levels, which decline precisely with reproductive age. The authors acknowledge this in the discussion, but the SPF (specific pathogen-free) mouse model does not allow the hormonal and microbial contributions to be completely separated. Nor has it been demonstrated that EPS administered intravaginally effectively reach the endometrium in vivo.

This study fits well with the growing evidence on the role of the endometrial microbiome in reproduction, but it is worth noting that a recent multicentre clinical trial published in Nature Communications (Haahr et al., 2025, reference 23 in the article itself) failed to demonstrate an improvement in IVF outcomes following treatment targeting the vaginal microbiome. We are therefore dealing with a promising line of research that is still at the preclinical stage. There is a considerable gap between an exopolysaccharide that attenuates endometrial senescence in 11-month-old mice and a validated postbiotic treatment for women of advanced maternal age. The most immediate clinical implication is not therapeutic but conceptual: it reinforces the idea that uterine ageing is an independent factor from ovarian ageing in reproductive failure, and that the endometrium deserves specific attention in fertility treatment strategies.

This study offers a novel perspective on reproductive ageing by focusing on the role of the endometrium and its microbiota, an aspect that has been much less studied than ovarian ageing. The authors show that the abundance of Lactobacillus gasseri decreases with age and that a higher presence of bacteria of the genus Lactobacillus is associated with better outcomes following embryo transfer. Furthermore, through studies using cell cultures and animal models, they identify a possible biological mechanism by which postbiotics derived from L. gasseri could improve endometrial receptivity.

This is a study of high methodological quality, as it combines clinical observations with functional studies that help to understand the mechanisms involved. The results are consistent with the growing evidence suggesting that the endometrial microbiota may influence embryo implantation and expand our understanding of the possible role of the endometrium in reproductive ageing. However, it is important to note that the clinical part of the study demonstrates an association between microbiota composition and reproductive outcomes, but does not allow a causal relationship to be established. Furthermore, although the authors use different experimental approaches to support their conclusions, the beneficial effects of postbiotics have mainly been demonstrated in animal models; therefore, they cannot yet be directly extrapolated to clinical practice.

Another significant limitation is that the study includes a relatively small number of patients, all of whom were undergoing treatment for infertility, which may limit the generalisability of the results. Furthermore, reproductive ageing is a complex, multifactorial process involving numerous biological factors, so the endometrial microbiota likely represents only one part of the process.

Overall, this study makes an important contribution to a better understanding of the changes the endometrium undergoes with age and opens up a very promising line of research into the potential use of postbiotics to improve endometrial receptivity. However, before any clinical application can be considered, prospective studies and clinical trials will be needed to confirm both the efficacy and safety of these interventions in women.