Dysbiosis of Gut Microbiota (DOGMA) – A novel theory for the development of Polycystic Ovarian Syndrome Original paper

What Was Reviewed?

This paper proposed a novel etiological framework termed the “Dysbiosis of Gut Microbiota (DOGMA) theory” to explain the development of polycystic ovary syndrome (PCOS). It reviewed both experimental and observational evidence linking gut microbiota imbalances to PCOS’s hallmark features: insulin resistance, hyperandrogenism, and anovulation. The authors synthesized findings from microbiology, endocrinology, gastroenterology, and immunology to argue that diet-induced dysbiosis triggers increased intestinal permeability, enabling the systemic translocation of lipopolysaccharides (LPS) from gram-negative bacteria. This metabolic endotoxemia, in turn, activates inflammatory pathways and disrupts insulin signaling, which they propose is the central mechanism leading to the hormonal and reproductive manifestations of PCOS. The paper also examined how probiotics, prebiotics, and synbiotics may represent novel, gut-targeted therapies for PCOS.

Who Was Reviewed?

The authors aggregated evidence from previous studies involving women with PCOS, obese individuals, those with irritable bowel syndrome (IBS) or chronic fatigue syndrome (CFS), and various animal models. These studies consistently demonstrated that individuals with PCOS tend to have poor dietary patterns, high in saturated fats and refined sugars but low in fiber, which promote gut dysbiosis and increased gut permeability. Although the paper did not report new microbiome sequencing data, it drew from prior literature that had established correlations between reduced levels of beneficial bacteria such as Bifidobacterium and Lactobacillus, and increased abundance of pro-inflammatory gram-negative species such as Enterobacteriaceae and Bacteroides.

What Were the Most Important Findings?

The paper’s central hypothesis, DOGMA, asserts that dysbiosis-induced increases in intestinal permeability initiate a cascade of systemic inflammation and insulin resistance that ultimately disrupts ovarian function. Specifically, the increased translocation of LPS into the bloodstream activates macrophages, leading to overproduction of TNF-α and IL-6, which impair insulin receptor signaling and raise systemic insulin levels. This hyperinsulinemia enhances androgen production by ovarian thecal cells and suppresses hepatic SHBG production, thereby increasing circulating free androgens. In parallel, insulin resistance blocks ovulatory follicle maturation, leading to menstrual irregularity and the characteristic polycystic ovarian morphology. The major microbial associations (MMA) discussed include a decline in Bifidobacterium and Lactobacillus, increased Escherichia coli and Bacteroides, and decreased production of short-chain fatty acids like butyrate, which are critical for maintaining mucosal barrier integrity. These findings collectively map a plausible causal pathway from gut microbial imbalance to endocrine dysfunction in PCOS, even in lean individuals.

What Are the Implications of This Review?

The DOGMA hypothesis marks a paradigm shift in PCOS pathophysiology, positioning the gut microbiome not as a secondary player, but as a central driver of disease onset and progression. For clinicians, this reframing has significant implications. It suggests that microbial screening could become part of diagnostic protocols for PCOS, especially in cases not explained by obesity or conventional metabolic syndrome criteria. Therapeutically, this review underscores the potential of prebiotics and probiotics to restore microbial balance, reduce metabolic endotoxemia, and reverse insulin resistance. While empirical support for these interventions in PCOS remains preliminary, the mechanistic rationale is robust, especially given successful outcomes in adjacent conditions like gestational diabetes and obesity.