Oral versus vaginal Lactobacillus supplementation for endometrial dysbiosis: A paired pre and post–endometrial microbiome study
- 1Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
- 2Tsubaki Women's Clinic, Matsuyama, Ehime, Japan.
Abstract
Infertility is a global health challenge, and impaired endometrial receptivity remains an important contributor to treatment failure. Endometrial dysbiosis, characterized by a low proportion of Lactobacillus in the endometrial microbiota, has been proposed as a potentially modifiable factor that may affect endometrial receptivity and fertility, and treatment with Lactobacillus-containing probiotics is emerging as a promising therapeutic approach. However, the optimal route of Lactobacillus supplementation remains unclear. We compared oral versus vaginal supplementation using the same Lactobacillus-containing formulation as an adjunct to standardized doxycycline/metronidazole therapy and continued oral lactoferrin in patients with baseline endometrial Lactobacillus <10%, based on paired microbiome profiling of endometrial samples (aspirated intrauterine fluid and endometrial tissue). In this single-center retrospective cohort study, thirty-two patients underwent paired endometrial microbiome testing before and after 30 days of supplementation (oral, n = 18; vaginal, n = 14). In the vaginal group, the median endometrial Lactobacillus proportion increased from 0.05% [0.00–0.20] to 99.15% [70.45–100.00] (p = 0.001), whereas in the oral group it increased from 0.00% [0.00–0.18] to 0.30% [0.03–66.33] (p = 0.005). The median change was greater with vaginal versus oral supplementation (+98.90% [70.45–99.80] vs + 0.25% [0.03–66.33], p < 0.001). Post-treatment Lactobacillus ≥80%, used as an exploratory marker of marked microbiota improvement, was observed in 9/14 patients (64%) in the vaginal group and 3/18 (17%) in the oral group (p = 0.010). Exploratory reproductive outcomes were limited by the small sample size and did not define a reliable clinical threshold. These findings suggest that, within this combined treatment regimen, vaginal Lactobacillus supplementation may provide a greater route-associated additional improvement in endometrial microbiota profiles than oral administration.
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BibTeX
@article{hiratsuka2026oral,
title = {{Oral versus vaginal Lactobacillus supplementation for endometrial dysbiosis: A paired pre and post–endometrial microbiome study}},
author = {Daiki Hiratsuka and Ayumi Iki and Mayu Kinoshita and Yumiko Doi and Okikaze Kato and Kotaro Oshima and Takehiro Hiraoka and Mitsunori Matsuo and Mari Ichinose and Tomoko Makabe and Gentaro Izumi and Miyuki Harada and Yasushi Hirota and Motowo Nabeta},
journal = {PLOS One},
year = {2026},
month = oct,
doi = {10.1371/journal.pone.0360619},
url = {https://doi.org/10.1371/journal.pone.0360619},
note = {CC BY},
}
RIS
TY - JOUR
TI - Oral versus vaginal Lactobacillus supplementation for endometrial dysbiosis: A paired pre and post–endometrial microbiome study
AU - Daiki Hiratsuka
AU - Ayumi Iki
AU - Mayu Kinoshita
AU - Yumiko Doi
AU - Okikaze Kato
AU - Kotaro Oshima
AU - Takehiro Hiraoka
AU - Mitsunori Matsuo
AU - Mari Ichinose
AU - Tomoko Makabe
AU - Gentaro Izumi
AU - Miyuki Harada
AU - Yasushi Hirota
AU - Motowo Nabeta
PY - 2026
DA - 2026/10/26
JO - PLOS One
DO - 10.1371/journal.pone.0360619
UR - https://doi.org/10.1371/journal.pone.0360619
AB - Infertility is a global health challenge, and impaired endometrial receptivity remains an important contributor to treatment failure. Endometrial dysbiosis, characterized by a low proportion of Lactobacillus in the endometrial microbiota, has been proposed as a potentially modifiable factor that may affect endometrial receptivity and fertility, and treatment with Lactobacillus-containing probiotics is emerging as a promising therapeutic approach. However, the optimal route of Lactobacillus supplementation remains unclear. We compared oral versus vaginal supplementation using the same Lactobacillus-containing formulation as an adjunct to standardized doxycycline/metronidazole therapy and continued oral lactoferrin in patients with baseline endometrial Lactobacillus <10%, based on paired microbiome profiling of endometrial samples (aspirated intrauterine fluid and endometrial tissue). In this single-center retrospective cohort study, thirty-two patients underwent paired endometrial microbiome testing before and after 30 days of supplementation (oral, n = 18; vaginal, n = 14). In the vaginal group, the median endometrial Lactobacillus proportion increased from 0.05% [0.00–0.20] to 99.15% [70.45–100.00] (p = 0.001), whereas in the oral group it increased from 0.00% [0.00–0.18] to 0.30% [0.03–66.33] (p = 0.005). The median change was greater with vaginal versus oral supplementation (+98.90% [70.45–99.80] vs + 0.25% [0.03–66.33], p < 0.001). Post-treatment Lactobacillus ≥80%, used as an exploratory marker of marked microbiota improvement, was observed in 9/14 patients (64%) in the vaginal group and 3/18 (17%) in the oral group (p = 0.010). Exploratory reproductive outcomes were limited by the small sample size and did not define a reliable clinical threshold. These findings suggest that, within this combined treatment regimen, vaginal Lactobacillus supplementation may provide a greater route-associated additional improvement in endometrial microbiota profiles than oral administration.
SN - 1932-6203
ER -