Validation of Synbiotics as a Microbiome-Targeted Intervention for Polycystic ovary syndrome (PCOS)

Overview

Synbiotic supplementation addresses both microbial imbalances and host inflammatory/pathological mechanisms associated with polycystic ovary syndrome (PCOS). PCOS is linked to various metabolic and inflammatory dysfunctions, including insulin resistance, hyperandrogenism, and obesity.^[1] These conditions are exacerbated by dysbiosis, where an imbalance in gut microbiota contributes to systemic inflammation and metabolic disturbances.^[2] Probiotic and prebiotic (synbiotic) treatments have demonstrated significant positive effects on restoring gut microbiota diversity and function, especially improving insulin sensitivity, lowering androgen levels, and reducing markers of inflammation like CRP (C-reactive protein).^[3] These effects reinforce the validity of synbiotics as a microbiome-targeted intervention (MBTI) by targeting gut dysbiosis, improving metabolic outcomes, and supporting the accuracy of PCOS’s microbiome signature​​.

Validation of Synbiotic Supplementation as an MBTI

Synbiotics, which combine probiotics and prebiotics, act through various molecular mechanisms. They modulate gut microbial composition, promote the growth of beneficial bacteria, and decrease pro-inflammatory species like Prevotella and Bacteroides.^[4] This rebalancing of gut microbiota supports a reduction in metabolic endotoxemia, a key contributor to insulin resistance and inflammation in PCOS. Clinical trials have shown that synbiotic supplementation significantly improves biomarkers of insulin sensitivity (such as HOMA-IR and serum insulin) and reduces androgen excess (total testosterone and free androgen index). Additionally, synbiotics enhance anti-inflammatory responses by reducing CRP levels and increasing the production of beneficial metabolites like nitric oxide​​.^[5]

Microbial Effects Summary Table

Validation of the Microbiome Signature of PCOS

PCOS is typically characterized by a microbiome with decreased diversity and an imbalance between beneficial microbes (like Lactobacillus and Faecalibacterium prausnitzii) and pro-inflammatory species such as Prevotella and Bacteroides. This dysbiosis contributes to the metabolic and inflammatory disruptions seen in PCOS, including insulin resistance and hyperandrogenism. Synbiotic supplementation targets this dysbiosis by promoting the growth of anti-inflammatory species like Bifidobacterium and Faecalibacterium, while reducing harmful microbes like Prevotella and Bacteroides. These shifts not only restore the microbiome balance but also improve metabolic outcomes such as insulin resistance, CRP levels, and testosterone concentrations, which are hallmark features of PCOS​.

Dual Validation

The microbial shifts observed following synbiotic supplementation in women with PCOS validate both the intervention as a microbiome-targeted therapy and the microbiome signature of PCOS. By increasing beneficial taxa such as Faecalibacterium prausnitzii and Bifidobacterium and decreasing pro-inflammatory taxa like Prevotella and Bacteroides, synbiotics help restore microbial balance. This not only addresses the underlying microbial dysbiosis in PCOS but also leads to significant clinical improvements, including reduced inflammation, improved insulin sensitivity, and normalization of androgen levels. These findings confirm the utility of synbiotics in managing PCOS and support the clinical relevance of its microbiome signature

References

1. Polycystic Ovary Syndrome: Etiology, Current Management, and Future Therapeutics. Singh S, Pal N, Shubham S, Sarma DK, Verma V, Marotta F, Kumar M.. (J Clin Med. 2023 Feb 11;12(4):1454)
2. Dysbiosis of Gut Microbiota (DOGMA) – A novel theory for the development of Polycystic Ovarian Syndrome. Tremellen, K., & Pearce, K. (2012).. (Medical Hypotheses, 79(1), 104–112.)
3. A New Approach to Polycystic Ovary Syndrome: The Gut Microbiota. Yurtdaş Depboylu, Gamze & Akdevelioğlu, Yasemin. (2019). (Journal of the American College of Nutrition. 39. 1-12)
4. The effects of synbiotic supplementation on hormonal status, biomarkers of inflammation and oxidative stress in subjects with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Nasri, K., Jamilian, M., Rahmani, E. et al.. (BMC Endocr Disord 18, 21 (2018))
5. The effects of synbiotic supplementation on hormonal status, biomarkers of inflammation and oxidative stress in subjects with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial. Nasri, K., Jamilian, M., Rahmani, E. et al.. (BMC Endocr Disord 18, 21 (2018))