Female reproductive tract - Gut axis: everything is connected

The female reproductive tract (FRT) and gut share bidirectional communication. These systems exchange not only microbes, but also metabolites, hormones, and immune signals that shape the vaginal microbiome.

What We Know:

• The FRT includes two regions: the lower tract (vulva, vagina, ectocervix) and the upper tract (endocervix, uterus, fallopian tubes, and ovaries). Recent studies support the existence of axes connecting the vagina to other organs, including the gut–vagina axis and bladder–vagina axis (Takada et al, 2023).

• Microbial overlap between the gut and vagina is common. Genetic comparisons of Lactobacillus crispatus and L. rhamnosus from both sites suggest they undergo site-specific adaptation. Strains show different gene expression profiles and traits—like stress tolerance, growth rate, adhesion, and fermentation—depending on their body location (Pan et al, 2020).

• Short-chain fatty acids (SCFAs) produced by microbiota may influence vaginal health. In the gut, SCFAs support barrier integrity and have anti-inflammatory roles. In contrast, in the vagina, elevated SCFAs are linked to inflammation and microbiome imbalance (Amabebe et al, 2020).

• Host immune factors also play a role. Antimicrobial peptides (AMPs) secreted by epithelial and immune cells help regulate which microbes thrive in the vaginal environment—and microbial communities can influence immune responses in return.

• Advances in IgA-sequencing have shown that vaginal communities dominated by L. crispatus have a higher proportion of IgA-coated bacteria, which are thought to promote microbial stability (Breedveld et al, 2022).

• Research suggests that IgA-producing immune cells in the vagina originate from the gut (Kobayashi et al, 2024). These cells become activated in the intestine, migrate to the reproductive tract, and secrete Lactobacillus-specific IgA, which enhances colonization of beneficial strains. This points to a potential mechanism by which gut immunity shapes the vaginal microbiome (Takada et al, 2025).

Industry Impact and Potential:

• There’s growing interest in using oral probiotics to support vaginal health, especially through the gut–vagina axis. This route may offer a convenient and non-invasive way to influence the vaginal microbiome by modulating gut microbes and immune responses (Romeo et al., 2024).

• New tools like IgA-sequencing and multi-site microbiome profiling are making it possible to track how bacteria and immune cells interact across the gut and reproductive tract. These methods could help researchers and product developers identify which strains are most effective for long-term colonisation and immune support.

• At the same time, many vaginal probiotic products on the market lack solid clinical evidence or regulatory backing. This highlights the need for better-designed studies and validated products that can actually deliver on their health claims.

Our Solution:

At Sequential, we support microbiome product development and testing from our global hubs in Cambridge, New York, and Singapore. Our flexible services help businesses innovate with confidence—ensuring their products maintain microbiome integrity while meeting efficacy and sustainability targets. We collaborate on studies exploring the FRT–gut microbiome axis and work with partners to develop impactful, science-backed solutions that improve health outcomes.

References:

Amabebe, E. and Anumba, D.O.C., 2020. Female gut and genital tract microbiota-induced crosstalk and differential effects of short-chain fatty acids on immune sequelae. Frontiers in Immunology, 11, p.2184. https://doi.org/10.3389/fimmu.2020.02184

Breedveld, A.C., Schuster, H.J., van Houdt, R., Painter, R.C., Mebius, R.E., van der Veer, C. and van Egmond, M., 2022. Enhanced IgA coating of bacteria in women with Lactobacillus crispatus-dominated vaginal microbiota. Microbiome, 10, p.15. https://doi.org/10.1186/s40168-021-01198-4

Breedveld, A. and van Egmond, M., 2019. IgA and FcαRI: Pathological roles and therapeutic opportunities. Frontiers in Immunology, 10, p.553. https://doi.org/10.3389/fimmu.2019.00553

Kobayashi, O., Taguchi, A., Nakajima, T., Ikeda, Y., Saito, K. and Kawana, K., 2024. Immunotherapy that leverages HPV-specific immune responses for precancer lesions of cervical cancer. Taiwanese Journal of Obstetrics and Gynecology, 63, pp.22–28. https://doi.org/10.1016/j.tjog.2023.10.002

Pan, M., Hidalgo-Cantabrana, C. and Barrangou, R., 2020. Host and body site-specific adaptation of Lactobacillus crispatus genomes. NAR Genomics and Bioinformatics, 2(1), lqaa001. https://doi.org/10.1093/nargab/lqaa001

Romeo, M., D’Urso, F., Ciccarese, G., Di Gaudio, F. & Broccolo, F., 2024. Exploring oral and vaginal probiotic solutions for women’s health from puberty to menopause: a narrative review. Microorganisms, 12(8), p.1614. https://doi.org/10.3390/microorganisms12081614

Takada, K., et al., 2023. Female reproductive tract–organ axes. Frontiers in Immunology. https://pmc.ncbi.nlm.nih.gov/articles/PMC9927230/

Takada, K., et al., 2025. IgA and the gut–vagina axis. Frontiers in Immunology. https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1547303/full