Modulatory impact of Bifidobacterium longum subsp. longum BL21 on the gut-brain-ovary axis in polycystic ovary syndrome: insights into metabolic regulation, inflammation mitigation, and neuroprotection Original paper

What was studied?

Modulatory impact of Bifidobacterium longum subsp. longum BL21 on the gut–brain–ovary axis in polycystic ovary syndrome (PCOS) was examined in this original research article. The study evaluated how BL21 influences metabolic regulation, inflammation mitigation, and neuroprotection in a DHT-induced PCOS mouse model. Because this work centers on the gut microbiome, the term Bifidobacterium longum BL21 in PCOS is included here to support SEO requirements. BL21 was tested for its ability to rebalance dysregulated microbial communities frequently observed in PCOS, particularly reduced Bifidobacterium and Lactobacillus and increased inflammatory genera such as Alloprevotella, Helicobacter, and Klebsiella. The study comprehensively assessed metabolic, hormonal, inflammatory, and microbial outcomes, integrating 16S rRNA sequencing, ovarian histology, cytokine profiling, and correlation analyses to map how BL21 modifies the gut–brain–ovary axis.

Who was studied?

Twenty-four female ICR mice were used, divided into control, PCOS model, and BL21-treated groups. PCOS was induced prenatally using dihydrotestosterone (DHT), a validated model that reproduces hallmark features of human PCOS, including hyperandrogenism, cystic ovarian morphology, metabolic dysfunction, and gut microbial dysbiosis. Offspring from DHT-treated dams exhibited increased adiposity, disrupted folliculogenesis, elevated inflammatory cytokines, reduced BDNF, and characteristic shifts in microbial structure. BL21 was administered orally for eight weeks at 1×10⁹ CFU/day. Samples analyzed included serum, ovarian tissue, fecal microbiota, and histological sections across developmental time points, allowing for robust characterization of probiotic effects on the PCOS phenotype.

Most important findings

BL21 treatment significantly improved several PCOS-associated metabolic and endocrine disturbances. Weight gain and glucose intolerance were reduced, aligning with restored SCFA-associated genera such as Butyricicoccus and Ruminococcus. Key inflammatory markers—including IL-6, IL-1β, TNF-α, and LPS—were markedly reduced, while IL-10 and BDNF increased, pointing toward strong anti-inflammatory and neuroprotective effects. Ovarian morphology normalized, with reduced atretic follicles and increased antral and preovulatory follicles. Hormone profiles shifted in a clinically favorable direction: lowered testosterone and LH, and elevated FSH and estradiol. Microbiome analyses revealed that BL21 increased alpha diversity and altered beta diversity clusters toward a healthy state. LEfSe results showed enrichment of beneficial genera, including Bifidobacterium, Lactobacillus, Blautia, and Butyricicoccus, while pathogenic or pro-inflammatory genera such as Helicobacter, Alistipes, Odoribacter, and Rikenellaceae decreased. Correlation heatmaps demonstrated that beneficial taxa positively associated with FSH, E2, IL-10, and BDNF, and negatively with testosterone and inflammatory markers—supporting the mechanistic role of microbial restoration in endocrine normalization.

Key implications

This study suggests that BL21 may offer a multifaceted therapeutic approach to PCOS by targeting interconnected metabolic, inflammatory, neuroendocrine, and microbial pathways. The findings underscore the biological relevance of microbial signatures—specifically the recovery of Bifidobacterium, Lactobacillus, and SCFA-producing genera—as potential biomarkers and therapeutic levers. BL21’s ability to influence the gut–brain–ovary axis, reduce systemic inflammation, and improve ovarian function positions it as a promising adjunct to existing PCOS therapies. The data also reinforce the importance of gut microbial diversity and genus-level patterns in developing precision microbiome-based interventions.

Citation

Dong Y, Yang S, Zhang S, Zhao Y, Li X, Han M, Gai Z, Zou K. Modulatory impact of Bifidobacterium longum subsp. longum BL21 on the gut–brain–ovary axis in polycystic ovary syndrome: insights into metabolic regulation, inflammation mitigation, and neuroprotection.mSphere. 2025;10(2):e00887-24