Polycystic Ovary Syndrome and the Bacterial Microbiome

I first learned about the concept of fecal microbiota transplant (FMT) a good 20 years ago, from my mentor who is a well-known functional medicine doctor.  I know some people are shocked by the idea but to me, it made sense from the get-go.  (For those unfamiliar, FMT means using stool (which is about made up of about 60% of bacteria from the intestines) to transfer bacterial contents.  Often it’s done via suppository, but nowadays, companies are working on purifying it into a non-noxious oral pill or solution.)

Many times, over the years, I’ve written about research and clinical studies using FMT on this blog.  As just one example, I wrote about a hugely successful study done on children with autism.  At this point (some studies in humans, some in animals), researchers have been able to transfer everything from the aforementioned autism to depression, anxiety, obesity, etc. by transferring the gut microbiome via FMT.

Thus, I was not all that surprised this morning to read about research recently conducted by scientists from China, the US’s National Institute of Health and Penn State University, in which they transferred polycystic ovary syndrome (PCOS) from humans to animals.[i]  For those of you not familiar with PCOS, it is a fairly common endocrine (hormone) disorder that affects women of reproductive age.  According to the Mayo Clinic, “Women with PCOS may have infrequent or prolonged menstrual periods or excess male hormone (androgen) levels. The ovaries may develop numerous small collections of fluid (follicles) and fail to regularly release eggs.”[ii]  It can not only cause incredibly unpleasant side effects for the affected woman (depression, anxiety, excess hair growth on the body, male-pattern balding, painful and prolonged periods, and more), it can also cause serious medical issues, including high blood pressure, gestational diabetes, infertility and miscarriage.  Research shows that this illness affects somewhere between 4% and 12% of women of reproductive age…which is a hell of a lot of women.[iii]

While the ultimate cause is unknown, low grade inflammation is known to be one of the contributing factors, and recently it’s been recognized that alterations in gut microbiome composition and gut barrier integrity (i.e. leaky gut) may play a major role in the development of PCOS.  The researchers involved in this study found that women with the syndrome had less bacterial diversity in their microbiomes, increased levels of the species, Bacteroides vulgatus, and a shift in genes affecting bile salts.[iv]

When they transferred the microbiome from affected humans to mice, the mice developed ovarian dysfunction, insulin resistance (a hallmark of PCOS), alterations in testosterone levels (another hallmark) and also had immunological changes including lowered levels of a cytokine called IL-22.  These bile acid changes and lowered levels of IL-22 are also seen in women with PCOS.  In fact, transferring just Bacteroides vulgatus to mice had the same effect.  The researchers state that this is the first evidence that gut microbiome alterations, and subsequent disruptions in bile acid synthesis, are directly responsible for the development of PCOS.

Giving the mice IL-22 and a bile acid (glycodeoxycholic acid) ameliorated the ovarian dysfunction and infertility, suggesting that this may potentially be a treatment for PCOS:  “This study suggests that modifying the gut microbiota, altering bile acid metabolism and/or increasing IL-22 levels may be of value for the treatment of PCOS.”  As there are no treatments right now, hopefully this new research will soon lead to one.  Will FMT end up being the answer for this illness?

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[i] Xinyu Qi, Chuyu Yun, Lulu Sun, et al. Gut microbiota-bile acid-interleukin-22 axis orchestrates polycystic ovary syndrome. Nat Med. 2019. doi: 10.1038/s41591-019-0509-0.

[ii] https://www.mayoclinic.org/diseases-conditions/pcos/symptoms-causes/syc-20353439

[iii] https://emedicine.medscape.com/article/256806-overview#a5

[iv] https://www.gutmicrobiotaforhealth.com/en/the-gut-microbiota-may-be-involved-in-ovarian-dysfunction-and-insulin-resistance-in-polycystic-ovary-syndrome/