Probiotic potential of <i>Parabacteroides johnsonii</i> in mitigating age-related ovarian functional decline

Dan-Yang Wang; Yin-Wei Wang; Ke-Chun Yu; Xuan Yang; Jun Ma; Bo-Han Li; Ya-Ling Peng; Xin-Yin Deng; Zhen-Xia Chen; Ling Wang

doi:10.1016/j.jgg.2026.03.023

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Probiotic potential of Parabacteroides johnsonii in mitigating age-related ovarian functional decline

doi: 10.1016/j.jgg.2026.03.023

Hubei Hongshan Laboratory, Hubei Key Laboratory of Metabolic Abnormalities and Vascular Aging, College of Life Science and Technology, College of Biomedicine and Health, Interdisciplinary Sciences Institute, Huazhong Agricultural University, Wuhan, Hubei 430070, China

Funds:

This work was supported by the National Natural Science Foundation of China (32470711).

Received Date: 2025-11-06
Accepted Date: 2026-03-25
Rev Recd Date: 2026-03-21

Available Online: 2026-04-02

Abstract

Abstract

The gut microbiota is increasingly recognized as a regulator of reproductive health, yet its role in ovarian aging remains unclear. Here, we combine Mendelian randomization (MR) analysis with experimental validation to investigate the causal relationship between gut microbiota and ovarian aging. MR analysis identifies four microbial taxa significantly associated with age at natural menopause. In mouse models, germ-free mice exhibit accelerated ovarian functional decline, including reduced ovarian reserve and impaired folliculogenesis. Fecal microbiota transplantation (FMT) from young donors alleviates ovarian aging phenotypes, whereas FMT from aged donors exacerbates functional decline. Metagenomic analysis reveals species-level differences between young and ovarian-aging mice, with Parabacteroides johnsonii (P. johnsonii) enriched in young mice. Administration of P. johnsonii to middle-aged mice improves ovarian reserve, reduces follicular atresia, enhances granulosa cell proliferation, and decreases systemic inflammation. These findings highlight a causal role of the gut microbiota in ovarian aging and support microbiota-targeted interventions as a potential strategy to preserve ovarian function.
- Gut microbiota,
- Ovarian aging,
- Fecal microbiota transplantation,
- Parabacteroides johnsonii,
- Mendelian randomization,
- Probiotic intervention

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