How Traditional Chinese Medicine can reshape the gut microbiome to alleviate insulin resistance in PCOS

How Traditional Chinese Medicine can reshape the gut microbiome to alleviate insulin resistance in PCOS

By linking intestinal barrier dysfunction, inflammation, and microbial metabolites to insulin resistance, this review examines whether traditional Chinese medicine could provide microbiome-targeted strategies for the treatment of PCOS and why stronger clinical evidence is urgently needed.

In a current review article published in the journal Frontiers in Nutrition was published, a group of authors summarized how Traditional Chinese Medicine (TCM). Gut microbiota (GM) could modulate insulin resistance (IR) in polycystic ovary syndrome (PCOS) and outlined potential, but as yet unvalidated, translating pathways for clinical care.

background

PCOS affects 5-20% of women of childbearing age and is often associated with IR, weight gain, irregular or absent menstrual cycles, and difficulty conceiving. Current drug treatments may be limited by side effects, costs, and concerns about long-term safety, as well as concerns about future risks Type 2 diabetes and heart disease due to these risk factors.

Recent research has shown a connection between our GM and the regulation of metabolism and hormones, as GM imbalance can affect intestinal permeability, trigger inflammation and increase IR.

TCM is widely used as a complementary and alternative therapy and is integrated into some regional clinical guidelines as a complementary approach. Future studies are needed to elucidate the mechanisms of action and develop standardized, safe and effective TCM protocols.

Why the gut is important in PCOS

PCOS is a metabolic and reproductive disorder that includes hyperandrogenism (HA), anovulation, and IR. IR leads to hyperinsulinemia (HI), which causes the ovaries to produce higher amounts of androgens, reduces the levels of sex hormone binding globulin (SHBG) in the liver, and alters the neuroendocrine network to increase production of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH).

In addition, the hypothalamic-pituitary-adrenal (HPA) axis can increase the production of adrenal androgen via adrenocorticotropic hormone (ACTH). Together, these systems exacerbate the metabolic and reproductive dysfunctions associated with PCOS.

New evidence suggests that GM may contribute by showing reduced diversity and fewer short-chain fatty acid (SCFA)-producing strains, along with increased numbers of endotoxin-rich organisms in women with PCOS and IR.

Barrier damage and microbial metabolites in PCOS

A healthy intestinal barrier relies on tight junction proteins such as occludin and zonula occludens-1 (ZO-1) to prevent microbial products from entering the bloodstream. In dysbiosis, permeability increases, resulting in a "holey gut" that activates lipopolysaccharide (LPS) and triggers cluster of differentiation 14 (CD14), toll-like receptor 4 (TLR4) complex, as well as myeloid differentiation major response 88 (MyD88) and nuclear factor kappa B (NF-κB). This drives tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6), which impair insulin receptor signaling via suppressor of cytokine signaling 3 (SOCS-3) and insulin receptor substrate 1 (IRS-1), aggravating IR. SCFAs and secondary bile acids normally support glucagon-like peptide 1 (GLP-1) secretion and metabolic control but are often reduced in PCOS.

Traditional Chinese Medicine routes connecting the gut and host metabolism

TCM is designed to promote gut-host interactions through five mechanisms, rather than established clinical pathways. First, in preclinical and small clinical studies, multiherb formulas remodel GM, improve intestinal barrier integrity, and inhibit LPS, TLR4, and NF-κB signaling, thereby promoting SCFA-producing bacteria, estrous cycles, and reduced inflammation.

Second, targeted phytochemicals and polysaccharides, including berberine, naringenin, Dendrobium officinale, Cordyceps, Astragalus spp., mangiferin, and curcumin, have been shown to reduce IR and increase the expression of occludin and ZO-1, primarily in animal models and limited human studies.

Third, dietary therapies, e.g. Some foods, such as quinoa and flaxseed oil, promote populations of Lactobacillus, Bifidobacterium, and Faecalibacterium, suggesting potential benefits for women with PCOS.

Fourth, probiotics, prebiotics, and synbiotics can help regulate either LH or follicle-stimulating hormone (FSH) ratios or inflammatory cytokine levels, with Bifidobacterium spp. with hormonal modulation and inulin are associated with a reduction in inflammation and IR.

Fifth, electroacupuncture has shown improvements in visceral adiposity and glucose tolerance in animal models. Clinical studies suggest that acupuncture combined with clomiphene may improve hormonal and metabolic outcomes compared to clomiphene alone. Acupuncture has also been reported to cause fewer gastrointestinal side effects than metformin in some studies.

Relevance in practice and security gaps

Patients with PCOS require management strategies that are adaptive, long-term and individualized. Microbiome-informed TCM approaches have been suggested to increase Fiber intake, targeted prebiotics or synbiotics, and formula-based interventions under clinical supervision. Yet the quality of evidence remains uneven.

Many clinical trials are small or short in duration, formulations vary significantly, and long-term safety, standardization, batch-to-batch consistency, and identification of active ingredients are limited.

The next step is multicenter randomized trials with harmonized diagnostic criteria, validated microbial endpoints, and omics-guided mechanistic studies to identify who benefits from which interventions and at what doses.

Conclusion

This review shows that GM may be a modifiable factor affecting IR and symptom severity in PCOS.

By repairing the intestinal barrier, reducing inflammation and LPS activity, restoring SCFA production, and engaging bile acid signaling pathways, TCM has shown the potential to improve metabolic and reproductive outcomes through a combination of approaches including herbal formulas, bioactive compounds, dietary therapies, prebiotics, synbiotics, probiotics, and acupuncture.

However, to translate TCM into practical clinical care, larger clinical trials, standardized herbal products, rigorous quality control frameworks, robust dose-response assessments, and ongoing safety assessments are required.

Therefore, the microbiome-based evidence for TCM needs to be strengthened and carefully translated into accessible, equitable and reliable care for individuals diagnosed with PCOS.

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