The Connection Between Gut Health and PCOS
Article Written By Laura Pollard
PCOS is a very complicated syndrome associated with numerous irritating and tedious symptoms; however the exact causes for PCOS, are obscure to us. There are many theories to what triggers PCOS, including genetic and environmental factors. One such theory, relatively new and currently being explored in the world of medical science, is the theory that an imbalance of microbes in the gut can trigger the development of PCOS.
While some microbes are pathogenic to us, there exists a wealth of microorganisms (MOs) that help us carry out many of our bodily functions and protect us from the “bad” MOs. In fact there are about as many bacterial cell in the human body as there are human cells. A recent study found that there are approximately 38 trillion bacterial cells, with a resulting mass of roughly 0.2kg, and 30 trillion human cells in the average 70kg man aged 20-30- with small quantitative variations for women [1]. Most bacterial cells reside within the gastrointestinal (GI) tract where they function to protect us against bad bacteria, aid in biochemical signaling, and assist us by increasing the nutrition value in much of the food we eat [2][7]. The imbalance, or maladaptation, of microorganisms in the gut- otherwise referred to as dysbiosis of the gut- seems to bea ‘hot topic’ in health science world [2][3].
What is Dysbiosis of the gut and what does it do?
We have a symbiotic relationship with our normal flora, or “good bacteria”, where we act as their host and they facilitate many of our bodily processes. What constitutes as our gut microbia is largely determined at birth and during the first three years of life, where exposure to the mother’s normal flora and the environment determine the phylogenic contents of our adult gut microbiota [2]. “Good” bacteria helps us in a number of different ways including displacing “bad bacteria”, assisting us in the breaking down of larger molecules so that they may be safely absorbed into our blood stream, and producing certain chemicals, such as serotonin, that we may use for various processes throughout our bodies [2][3]. In order for these bacterial to thrive me must produce a favorable environment for them; otherwise “bad’ bacteria may over populate, causing a microbia imbalance, or dysbiosis of the gut.
So what happens when our GI tract’s normal flora has been disrupted? When we partake in a diet that consists of low fiber and highly processed foods-as well as excessive alcohol consumption- our good bacteria become “uncomfortable”, they no longer have theirprefered food source and the pH in the GI tract increases, making it a more favorable environment for “bad bacteria”[3]. If an adversediet is eaten regularly for a long period of time, the ratio of “good” to “bad” bacteria will likely decrease to a point where the byproducts of the “bad” bacteria will reduce the integrity of the GI tract wall. When the wall of the GI tract is compromised, its permeability increased and large molecules, originally not meant to pass between the epithelial cells of the GI wall, are able to enter the blood stream and create a number of unfavorable responses [3]. Additionally, with limited “good” bacteria available to help us break down certain molecules, nutrients are more scarcely available and less like to be absorbed into the blood stream [2][3].
How does dysbiosis of the gut relate to PCOS?
Although there has consistently been some debate regarding what constitutes PCOS, two biochemical factors have always been in agreement and witnessed in most women with the conditon: the presence of chronic inflammation and insulin resistance (metabolic dysfunction) [3]. Many studies have found a correction between gut microbiota and metabolic dysfunction, where it is said that mediators of the brain-gut axis – by which messages are sent between the central nervous system and the GI tract- may be regulated by “good” bacteria [3]. One study found that women with PCOS had higher levels of certain “bad” bacterial strains in their stool sample than non-PCOS women; this demonstrated a positive correlation with BMI and testosterone in women with PCOS [4]. Additionally, low levels of the leptin hormone may be associated with a reduction of “good” bacteria in the GI tract. Leptin- which functions to regulate appetite, promote the dominance of Th1 cells over Th2 cells and preventing the proliferation of Treg, and preserve thymic function- has been associated with nutrient deprivation that is often worsen when there is a lack of “good” bacteria in the GI tract [2]. In turn, the low levels of the leptin hormone has been associated with the less efficient activation of certain immune cells, which would typically preventintestinal wall destruction due to a severe and prolonged inflammatory response within the GI tract[2].
In recent years a new concept, referred to as microgenderome, reveals a potential relationship between sex hormones and gut microbiota[5]. At this time, the studies encompassing the microgenderome concept are largely animal based; non-the-less these studies are significant stepping stones in discovering connections between hormone concentrations and gut microbiota in humans. For example one study showed that the removal of gut microbiota was followed by a decrease in testosterone in male mice but an increase in testosterone in female mice [6]. Another study found that rats with PCOS demonstrated improved esterous cycles and a decrease in the biosynthesis of androgens in all rats when treating them with a probiotic and “fecal microbia transplant” and 75% of the rats treated with probiotic transplant [5]. While most microgenderome studies have be conducted with mice and rats, there are a number of studies that have be conducted that may indirectly explain the association between gut health and hormone regulation.
The imbalance between “good” and “bad” bacteria within the gut can potentially affect the exacerbation, and possibly the development, of PCOS in a number of different ways. “bad” bacteria contain what is known as lipopolysaccharide (LPS), a known stimulant of inflammation, on their cell wall[2]. Inflammation in the GI tract is able to increase the permeability of the GI tract walls via compromising the integrity of the ‘tight junction’ proteins that keep the wall cells tightly bound [2][3]. Inflammatory promoting factors are then released in the blood stream; these factors have been associated with the inactivation of insulin receptors on our cells, preventing insulin from binding its respective receptor; thereby preventing glucose from entering a cell to be used as fuel [2][3]. An increase in blood insulin levels, as well as the increase in certain inflammatory factors, trigger a rise in androgen production from the theca cells of the ovaries[3]. High levels of blood insulin also reduces the Sex Hormone Binding Globilin (SHBG) released from the liver which allows more free, bioavailable, testosterone to exist throughout the body[2]. Prolonged inflammation further weakens tight junctions creating a positive feed-back loop. Therefore, it stands to reason that that dysbiosis of the gut has the potential to make serious contributions to the development and aggravation of PCOS.
What can women with PCOS do?
There are a number of treatments offered to women with PCOS that range from invasive to non-invasive; one non-invasive and common practice is to control the condition through diet and exercise. One’s diet is especially important if the aim is to bring balance to one’s gut microbiota. While little or no studies have been conducted to examine probiotics as a treatment for PCOS, adjusting the balance between good and bad bacteria has been shown to improve inflammation and insulin sensitivity in general. A healthy diet of unprocessed foods, limited alcohol, and high fiber will help to produce an environment for good bacteria to thrive [7]. Additionally a good probiotic supplement will help to jumpstart gut microbial replenishment and should be taken regularly when receiving antibiotic therapy.
References
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- Kau A L, Ahem P P, Griffin N W, Goodman A L, Gordon J I (2011). Human nutrition, the gut microbiome and the immune system. Nature. 474 (7351): 327–336. doi:10.1038/nature10213
- Tremellen K, Pearce K (2012) Dysbiosis of Gut Microbiota (DOGMA) - A Novel Theory for the Development of Polycystic Ovarian Syndrome. Medical Hypotheses 79:104-112.
- Guo Y, Qi Y, Yang X, Zhao L, Wen S, Liu Y,et al. (2016) Association between Polycystic Ovary Syndrome and Gut Microbiota. PLoS ONE 11(4):e0153196. doi:10.1371/journal.pone.015319
- Liu R, Zhang C, Shi Y, Zhang F, Li L, Wang X, et al.(2017) Dysbiosis of Gut Microbiota Associated with Clinical Parameters in Polycystic Ovary Syndrome. Front. Microbiol. 8:324. doi: 10.3389/fmicb.2017.00324
- Markle JG, Frank DN, Mortin-Toth S, Robertson CE, Feazel LM, Rolle-Kampczyk U, et al. (2013) Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity. Science. 339(6123):1084-8. doi:10.1126/science.1233521PMID:23328391
- Rowland I, Gibson G, Heinke A, Scott K, Swann J, Thiele I, Tuohy K (2017) Gut Microbiota functions: metabolism of nutrients and other food components. Eur J Nutr. doi:10.1007/s00394-017-1445-8