Gut Microbiome and Menopause / Perimenopause

Menopause is not simply the end of a woman’s reproductive phase. It is a complex transitional period characterized by extensive hormonal, immunological, and metabolic changes that affect the body's overall functioning.

During perimenopause, that is, the transitional phase preceding menopause, characterized by pronounced fluctuations in female hormones before the permanent cessation of menstruation, as well as during menopause itself, many women experience symptoms such as fatigue, weight gain, bloating, bowel disturbances, mood changes, and reduced sleep quality. These symptoms are often attributed exclusively to hormonal changes, without consideration of a critical regulatory factor of health: the gut microbiome.

The gut microbiome, defined as the total population of microorganisms residing in the gastrointestinal tract, plays an active role in regulating metabolism, immune responses, and inflammation, as well as hormonal balance. During the menopausal transition, the decline and fluctuations in estrogen levels are accompanied by significant changes in both the composition and function of the microbiome.

These changes are not random. They reflect a dynamic biological dialogue between the endocrine and immune systems, with the gut acting as a central regulator of this process. Disruption of this balance may lead to increased intestinal permeability, low-grade inflammation, and metabolic dysfunctions, directly affecting a woman’s quality of life as well as her long-term risk of developing chronic diseases.

Understanding the relationship between the gut microbiome and menopause is now a fundamental pillar of a modern preventive approach to women’s health, highlighting the gut as a central regulator of balance during this transitional period.

Gut Microbiome and Menopause: Biological Mechanisms of Interaction

The gut microbiome consists of trillions of microorganisms, primarily bacteria, that coexist within the digestive system and perform fundamental functions essential to human health. These microorganisms contribute to the breakdown and absorption of nutrients, the synthesis of vitamins, defense against pathogenic agents, and the regulation of both the immune and endocrine systems.

During menopause, hormonal changes are not limited to declines in estrogen and progesterone; they are also accompanied by substantial alterations in the composition and function of the gut microbiome. Disruption of this balance, known as dysbiosis, has been associated with the development of multiple gastrointestinal, metabolic, and systemic symptoms observed during this transitional period.

Estrogens and the Microbiome: A Bidirectional Biological Axis

Estrogens directly influence gut function by regulating intestinal motility, intestinal mucosal permeability, and microbiome composition. At the same time, the gut microbiome does not act passively; it actively participates in estrogen metabolism through the so-called estrogen-microbiome axis, known as the estrobolome.

Certain bacterial strains possess enzymes that enable the deconjugation and reabsorption of estrogens from the intestine, thereby influencing their bioavailability in systemic circulation. When the function of this axis is disrupted, the following may be observed:

reduced reabsorption of estrogens
imbalance among estrogen forms E1, E2, and E3
clinical manifestations affecting the skin, urinary tract, and central nervous system

At the same time, during menopause, declining estrogen levels are associated with:

reduced microbial diversity
increased abundance of strains linked to inflammatory processes
decreased populations of protective bacteria, such as Lactobacillus and Bifidobacterium

Dysbiosis, Intestinal Permeability, and Inflammation

The above changes in microbiome composition directly affect the integrity of the intestinal barrier. Increased intestinal permeability (“leaky gut”) allows bacterial components, such as lipopolysaccharides (LPS), to enter the bloodstream.

The presence of these molecules activates the immune system, leading to chronic, low-grade inflammation. This inflammatory burden is not confined to the gut but affects multiple organ systems, including the liver, brain, and cardiometabolic axis.

Perimenopause as a Biological Stressor

Perimenopause is characterized by intense and often unpredictable hormonal fluctuations, a phenomenon that acts as a significant biological stressor for the gut microbiome. Research data indicate that this transitional period affects not only the large intestine but also the small intestine, intensifying symptoms such as bloating, gas, postprandial fatigue, and neuroendocrine disturbances.

The accumulation of these changes creates an inflammatory microenvironment that promotes:

increased visceral fat accumulation
development of insulin resistance
impaired microcirculation
worsening mood and the emergence of depressive symptoms

Understanding these biological mechanisms highlights the gut microbiome as a key regulator of health during menopause and lays the foundation for a causal, preventive approach to women’s healthcare.

Functional Medicine and the Gut Microbiome in Menopause

Functional medicine approaches menopausal changes not as isolated symptoms, but as the result of interacting biological mechanisms. The gut functions as a central regulator, as the integrity of the intestinal barrier, the composition of the microbiome, and their relationship with hormones and the immune system collectively influence metabolic and neuroendocrine balance. Within this framework, the functional approach focuses on three core pillars:

Identification and interpretation of biological imbalances. Assessment includes evaluation of gut function, inflammatory status, nutritional adequacy, and hormonal balance, with the aim of linking clinical symptoms to their underlying mechanisms.
Personalized support. Intervention is not based on generalized protocols, but is tailored to each woman’s individual biological profile, considering microbial balance, inflammatory burden, and metabolic needs.
Monitoring and adjustment. Functional medicine is a dynamic process. Regular reassessment allows optimization of the approach, with the goal of gradually restoring functional balance.

Specialized functional medicine testing enables detailed mapping of the biological disturbances that accompany menopause, offering a comprehensive view of gut, metabolic, and hormonal function. Indicatively:

EnteroScan® Gut Microbiome Analysis: Analyzes the composition and function of the gut microbiome, identifies deviations in microbial flora and markers of intestinal inflammation or permeability, and contributes to investigating the etiology of gastrointestinal and systemic conditions.
MenoScan® Comprehensive Menopause Profile (salivary hormonal profile): Provides an in-depth evaluation of hormonal status during perimenopause and menopause, offering a comprehensive picture of steroid hormone balance.
ImmuneScan® Chronic Inflammation Assessment: Evaluates systemic inflammatory burden, providing critical insights into immune function and balance.
FemoScan® Vaginal Microbiome Assessment: Evaluates vaginal microbial balance, which may influence urogenital health, inflammatory processes, and symptoms associated with hormonal changes.

Nutrition and Lifestyle to Support the Microbiome During Menopause

Daily life during perimenopause and menopause changes, and, along with it, dietary and functional choices must also be adapted. Targeted changes in nutrition and lifestyle can reduce inflammation, support gut microbial balance, and alleviate symptoms associated with declining estrogen levels.

Nutrition: The Primary Functional Tool

1. Dietary fiber – nourishment for beneficial bacteria. Prebiotic fibers enhance the production of short-chain fatty acids (SCFAs), such as butyrate, which reduce inflammation and strengthen the intestinal barrier. Sources of dietary fiber that support the microbiome include:

Legumes (peas, lentils, beans)
Leeks, garlic, onions, bananas
Oats, quinoa, flaxseed

2. Polyphenols – natural antioxidants. Polyphenol-rich foods promote the growth of beneficial bacteria such as Akkermansia muciniphila and Faecalibacterium prausnitzii, which are associated with anti-inflammatory effects and metabolic balance. Indicatively:

Pomegranate, blueberries, cherries
Cocoa (preferably unsweetened)
Green tea and extra virgin olive oil

3. Fermented foods – natural probiotic support. Fermented foods directly increase microbial diversity and support gut function. Possible options include:

Kefir, fermented milk, probiotic yogurt
Fermented vegetables without vinegar
Miso and tempeh

4. Limiting processed foods and sugar. Foods with a high glycemic load and added sugars promote inflammation and dysbiosis. It is recommended to avoid or limit:

Processed cereals and snacks
Sugar-sweetened beverages or those with artificial sweeteners
Fried foods and trans fats

Supplementation Based on Diagnosis
The use of supplements is not a general recommendation but should be implemented only after individualized assessment and in collaboration with a healthcare professional. Indicatively:

Probiotics (e.g. Lactobacillus reuteri, L. plantarum): support estrogen balance and may reduce hot flashes
Glutamine and zinc carnosine: contribute to restoration of the intestinal barrier
Vitamins D3 and K2: regulate inflammation and support bone health

Functional Lifestyle

Sleep: Sleep disruption is associated with dysregulation of the microbiome and increased inflammation. The goal is 7.5–8 hours of quality sleep. A consistent evening routine without screens, or the use of low-dose melatonin only when necessary, may be beneficial.
Physical activity: Aerobic exercise and gentle forms of movement, such as yoga, 3–4 times per week, increase microbial diversity and reduce inflammatory burden.
Stress management: Chronic stress negatively affects the microbiome and increases intestinal permeability. Techniques such as mindfulness, diaphragmatic breathing, or meditation can help manage stress and, consequently, support gut health.

In Conclusion

Perimenopause and menopause are complex biological transitions that extend beyond hormonal changes and substantially affect the gut microbiome, inflammatory balance, and metabolic function. Alterations in the composition and functionality of the microbiome are associated with symptoms such as gastrointestinal discomfort, weight gain, mood disturbances, and increased cardiometabolic risk.

Contemporary scientific evidence highlights the gut as a central regulator of health during this transitional period, through its close interaction with the immune, endocrine, and nervous systems. Understanding these mechanisms provides the foundation for more targeted, personalized, and preventive approaches to women’s healthcare, with an emphasis on maintaining functional balance and overall well-being.

What you can do today:

Discover what’s truly happening in your body through EnteroScan® and MenoScan®, specialized functional analyses that offer a comprehensive overview of the biological mechanisms at the core of the interaction between the gut microbiome and the changes occurring during menopause and perimenopause.
See how Functional Medicine can help you in practice, by identifying root causes instead of just masking symptoms.
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References

Peters BA, Santoro N, Kaplan RC, Qi Q. Spotlight on the Gut Microbiome in Menopause: Current Insights. Int J Womens Health. 2022;14:1059-1072
https://doi.org/10.2147/IJWH.S340491
Lin, F., Ma, L. & Sheng, Z. Health disorders in menopausal women: microbiome alterations, associated problems, and possible treatments. BioMed Eng OnLine 24, 84 (2025). https://doi.org/10.1186/s12938-025-01415-3
Kim C, Asnicar F, Marples L, et al. Associations between gut microbiota and menopause symptoms: novel insights from the ZOE PREDICT 3 cohort. Proceedings of the Nutrition Society. 2025;84(OCE3):E243. doi:10.1017/S0029665125101122
Wang, H., Shi, F., Zheng, L., Zhou, W., Mi, B., Wu, S., & Feng, X. (2025). Gut microbiota has the potential to improve health of menopausal women by regulating estrogen. Frontiers in Endocrinology, 16, 1562332. https://doi.org/10.3389/fendo.2025.1562332

At Diagnostiki Athinon, we treat prevention with the seriousness it deserves. This is where science meets personalized care.