The Gut Microbiome’s Impact on Premenstrual Disorder

Premenstrual disorder (PMD) encompasses a spectrum of symptoms experienced by women in the luteal phase of the menstrual cycle, manifesting as physical, emotional, and behavioral changes that can significantly impact daily life. While the exact cause of PMD remains multifactored and complex, emerging research highlights the influential role of diet and the gut microbiome in modulating hormonal balance and mood regulation. Understanding the intricate relationship between the gut, diet, and PMD is crucial.

PMD, as its name suggests, occurs 2 to 7 days (and sometimes more) before period and stops when it begins or on the following days. PMD affects millions of women of all backgrounds. Recent studies establish that approximately 90% of women of childbearing age experience at least one mild symptom and that between 20-40%, the symptoms interfere with their daily activities¹. The most common symptoms of PMD include many manifestations, both physical and emotional. These symptoms are sore or tender breasts, headache, fatigue, skin changes, acne, irritability, mood swings, food cravings, and depression. There are also gastrointestinal (GI) symptoms such as intestinal pain and bloating, diarrhea or constipation². PMD is not associated with age, educational level, or revenue³. The pathophysiology of PMD is not clear, but experts link PMD with hormonal changes, serotonergic dysfunction, impaired gamma-aminobutyric acid (GABA) function, stress, and poor lifestyle habits such as longer durations of internet use and shorter sleep durations. Treatment of PMD includes prescribed drugs, such as oral contraceptives or serotonin reuptake inhibitors (with some adverse effects), lifestyle modifications (meditation, exercise, diet…). Dietary changes include consuming soy isoflavones and soy products, although not every woman is responsive to these natural compounds. A recent review concluded that diet is an essential modulating factor to manage PMD symptoms although clear and specific recommendations are difficult to conclude. It is suggested that calcium, magnesium, vitamins B & D, and some herbal supplements can be useful and effective to support quality of life and help to control some PMD symptoms³.

Role of Gut Microbiome in Premenstrual Disorder

The gut microbiome comprises trillions of microorganisms residing in the gastrointestinal tract, including bacteria, viruses, fungi, eukaryotic parasites, and archaea⁴. These microbes play a crucial role in host physiology, influencing nutrient metabolism, immune function, and neurological signaling. The composition and diversity of the gut microbiome are influenced by various factors, including diet, lifestyle, medications, and hormonal fluctuations.

An increasing number of studies are now linking PMD with imbalance of the gut microbiome. Dysbiosis, characterized by an imbalance in microbial composition and function, has been associated with increased inflammatory markers, hormonal imbalances, and neurotransmitter disturbances—all of which are implicated in PMD symptomatology. Moreover, dysbiosis can disrupt intestinal barrier integrity, leading to the translocation of microbial products and triggering systemic inflammation, further exacerbating PMD symptoms. Takeda et al. (2022) compared the structure of the fecal microbiome of women experiencing PMD that negatively affect their daily activities to women with no serious PMD (controls). Slight differences in microbiome were observed and the authors concluded that Parabacteroides and Megasphaera negatively predicted the more severe symptoms of PMD⁵. In another study comparing 24 Japanese women experiencing PMD with 144 healthy women, it was observed that alpha diversity was increased, and beta diversity was different in PMD group than the control group.

The composition of the fecal microbiome differs between women with PMD vs controls. After controlling for confounders, Collinsella spp. had the highest effect size in participants of 30-40 years of age⁶. But it is not just about who is there, i.e. what type of microorganism are part of the gut microbiome. The gut microbiome plays a pivotal role in the production of various metabolites, including S-(-)equol, short-chain fatty acids (SCFAs), neurotransmitters, and hormones. Interestingly, it has been shown that only about 30-60% of people have a gut microbiome able to produce S-(-)equol, a metabolite biotransformed from isoflavones by certain gut microbes. S-(-)equol has agonist-antagonist estrogen action, which contributes to improvement of PMD symptoms⁷. SCFAs (butyrate, acetate, and propionate), have anti-inflammatory properties and exert regulatory effects on immune function and synthesis of neurotransmitter. Furthermore, certain gut bacteria can produce neurotransmitters like serotonin, dopamine, and gamma-aminobutyric acid (GABA), which modulate mood, cognition, and behavior⁸. Dysregulation of these microbial metabolites may contribute to the mood disturbances and cognitive changes observed in PMD.

There are many influences on Premenstrual disorder. From lack of sleep and extensive use screens to added stress and sedentary lifestyles. These lifestyles result in dysfunction in serotonergic and GABA transmitters and hormonal imbalance. By modifying one’s lifestyle to include exercise, mindfulness, and a healthy diet (including dietary diversity, high fiber, probiotics, etc.), this improves the gut microbiome, which supports neurotransmitter production and hormone balance.

Premenstrual Disorder and Probiotics

Some probiotics have been shown to synthesize metabolites such as SCFAs, neurotransmitters, and hormones. Probiotics have also been evaluated to alleviates symptoms of PMD. Many decades ago, in 1996, a study on sixteen women administered 3 capsules daily of a probiotic containing 1 billion of L. acidophilus NCDO 1748 and 1 billion of Bifidobacterium bifidum NCDO 2203 strains in combination with antidepressant drug (S-adenosyl-L-methionine) revealed modulation of their gut microbiome, normalization of enzymatic activities of fecal enzymes and relief of PMD symptoms, as observed in most participants⁹. More recently, in a study on 80 women experiencing PMD, women receiving 10 billion L. paragasseri OLL2809 daily had less irritability and greater change in premenstrual arousal score compared to placebo after three menstrual cycles¹⁰. Tablets of L. gasseri CP2305 was administered daily to 56 women over the course of 6 cycles. Overall, the probiotic group reported less PMD symptoms than placebo, including depressed mood and anxiety. Also, in this group, an increase in salivary estradiol and progesterone in the luteal phase was observed¹¹.

Unfortunately, the exact mechanisms of action (MoAs) of probiotics to alleviates symptoms of PMD is not clearly known. Action on the mucosal barriers and immune system to modulate gut inflammation, antimicrobial activity against pathogenic microbes, secretion of gut hormones, and neurotransmitters are some MoAs that have been associated with probiotics in this context. Lactobacilli and Bifidobacteria have been shown to biotransform dietary isoflovanes into S-(-)equol or dietary fibers in to SCFA, two types of metabolites that have been associated with better outcomes in PMD.

Conclusion

The gut microbiome exerts profound effects on various aspects of women’s health, including the pathophysiology of PMD. Dysbiosis-driven inflammation, hormonal dysregulation, and alterations in neurotransmitter signaling contribute to the complex symptomatology of PMD. More research in this field is needed to fully explain these complicated interactions so optimal treatments are available to relieve the symptoms of PMD. However, these initial research developments suggest that women who suffer from PMD may be able to manage their symptoms through dietary approaches to support their gut microbiome such as incorporating micronutrients, prebiotics, probiotics or probiotic-rich foods. By focusing on gut health, women can have a holistic and accessible approach to mitigate the symptoms of PMD, ultimately enhancing their quality of life.

• Mathieu Millette, Ph.D., Mcb. A.

  Graduated with honors from INRS-Armand-Frappier Institute, Dr Mathieu Millette is an authority on probiotics for over 20 years. Seasoned microbiologist, lecturer and Scientific Director for Kerry company, he leads a team of talented scientists dedicated to elucidate the mechanisms of action of probiotic bacteria and to understand the interactions between beneficial microorganisms, the gut microbiome and the immune system. Mathieu Millette is also associate Professor at INRS-IAF and an active member of the Association of Microbiologists of Quebec and of the International Probiotic Association. Dr. Millette is author and co-author of over 50 peer-reviewed publications or book chapters and is the inventor of 3 patented applications.

• References
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