How Dysbiosis Might Be A Key Factor in PCOS
review of Senthilkumar H, Arumugam M. Gut microbiota: a hidden player in polycystic ovary syndrome. J Transl Med. 2025 Apr 15;23(1):443. doi: 10.1186/s12967-025-06315-7. PMID: 40234859; PMCID: PMC1199
Polycystic Ovarian Syndrome (PCOS) is the leading cause of infertility in women. As digestive specialist I have routinely seen ovulation and menstrual function improve in PCOS patients after we treat dysbiosis.
It is important to know that that patterns of PCOS are heterogenous; meaning that not all patients fit all the criteria that describes PCOS.
However there tends to be some dominant patterns:
Elevated Androgens (Free testosterone, DHEA-S)
Impaired Glucose Tolerance/ Insulin resistance
Difficulty with weight management. Although do know there are subsets of PCOS called Lean PCOS.
Anovulatory cycles.
In addition, there tends to be comorbidities like anxiety/stress dysregulation
So with great anticipation I reviewed the paper Senthilkumar H, Arumugam M. Gut microbiota: a hidden player in polycystic ovary syndrome. J Transl Med. 2025 Apr 15;23(1):443. doi: 10.1186/s12967-025-06315-7. PMID: 40234859; PMCID: PMC11998
As we test and find dysbiosis in our PCOS patients often, and when we treat it they often do better, but why?
This paper looked at Multiple cross-sectional and interventional studies
And these studies consistently showed gut microbiome changes in PCOS. These changes are distinctive, often contentious..yet not entirely understood .
They include:
increased Bacteroides, Escherichia/Shigella
Decreased Lactobacillus, Bifidobacterium, and Akkermansia.
In the studies, Dysbiosis correlated with hyperandrogenism, insulin resistance, and chronic inflammation via lipopolysaccharide (LPS) translocation, IL-6–CYP17A1 upregulation, and disrupted bile acid–IL-22 signaling.
Remember correlation does not mean causation
They looked at interventional Random Control Trials (RCT’s) of probiotics and synbiotics (e.g., Lactobacillus and Bifidobacterium species for 8–12 weeks) and these reported modest but significant improvements in HOMA-IR, triglycerides, and testosterone.
Of note, Fecal Microbial Transplant (FMT) studies in rodent PCOS models showed restoration of estrous cycles and lower androgen levels.
Here were the key mechanisms proposed:
Gut dysbiosis contributes to PCOS pathogenesis via multiple interconnected mechanisms:
Lipopolysaccharide( LPS)-induced inflammation activates IL-6 and CYP17A1, promoting ovarian androgen synthesis
Decreased IL-22 due to altered bile acid metabolism (Bacteroides vulgatus-mediated) impairs follicular development.
Reduced SCFAs lower GLP-1 and PYY, worsening insulin resistance and appetite control.
Also fascinating that the authors pointed out that studies have shown t that women with PCOS have lower levels of ghrelin and PYY ( Both indicating insulin resistance ) than healthy women.
They propose increase in Bacteroides species that are adversely linked with ghrelin.
It is pointed out that SCFAs stimulate GLP-1 and PYY release which improve insulin sensitivity , But in PCOS dysbiosis there are decreased SCFAs are reduced GLP-1/PYY which worsens insulin resistance.
Altered gut-brain axis signaling affects GnRH and LH secretion…which ultimately raises androgen levels and decreases FSH surges.
How does this change my practice:
I absolutely will be looking at bile-acid-profiles in my PCOS patients. I only know of a few tests out there that offer bile acid profiling and Vibrant America Gut Zoomer 3.0 seems to be the one that does that best. However , we are sorely lacking protocols of how to favorably alter bile-acid profiles. This is an area of major need.
I will also look at improving the Short Chain Fatty Acid pool in these patients through Prebiotic prescribing and dietary shifts to include Microbial Accessible Carbohydrates (MACS) and Resistant starches.
And, I will continue to test and address dysbiosis. The PCOS Dysbiosis pattern is no necessarily defined but some dysbiosis with pathobiont expansion would likely flag as significant as would small intestinal bacterial overgrowth.
These microbiome interventions pair well with other treatments we use for PCOS:
Insulin resistance: Liposomal berberine, myo-inositol (which work synergistically with improved SCFA production)
Egg quality & ovulation: NAC, myo-inositol (40:1 ratio with D-chiro-inositol)
Androgen management: Glycyrrhiza (licorice root) - with blood pressure monitoring
LH/FSH modulation: Vitex (primarily for hyperprolactinemic presentations)
Inflammation: NAC also provides antioxidant support for the LPS-driven inflammation discussed above”
The microbiome-gut work complements pharmaceutical approaches:
Metformin: Interestingly, metformin itself modulates gut microbiota (increasing Akkermansia), so treating dysbiosis may enhance metformin’s efficacy
GLP-1 agonists: These pharmacologically provide the GLP-1 that a healthy microbiome would naturally stimulate via SCFAs - addressing the problem from both ends. Note, I have not seen studies that actually indicate GLP-1 medications increase SCFA’s.
Spironolactone: Addresses androgen effects while microbiome work may reduce androgen production via the LPS-IL-6-CYP17A1 pathway
Oral contraceptives: Can be used alongside microbiome interventions for cycle regulation and androgen suppression; yet they have other microbiome concerns. (a topic for another time)
Ovulation induction agents (letrozole/clomiphene): May work better when insulin resistance and inflammation are addressed via microbiome optimization
The paper also mentioned a few other interventions to consider and keep an eye on Including, Dietary modifications (plant-based proteins increasing beneficial microbes), Postbiotics , FMT , and precision microbiome therapies including CRISPR-Cas9 approaches.
Any patient with PCOS; deserves to take a good look at their gut for clues .
We have covered PCOS a lot on my podcast and substack see other links below