Perimenopause, Brain Health and the Gut–Brain Axis: Understanding the Connection

Have you ever noticed that your digestion, mood, sleep and stress resilience seem to change together?

Maybe during a stressful week, your bloating worsens.

Maybe poor sleep leaves you feeling more anxious and less focused.

Or maybe during perimenopause, you have started noticing brain fog, forgetfulness, mood changes or reduced concentration alongside digestive changes.

While changing hormones are likely part of the picture, researchers are increasingly exploring another fascinating area of health: the gut–brain axis.

Emerging research suggests that hormones, the gut microbiome, the nervous system, immune signalling and brain function may all interact during the menopausal transition.

Gut–Brain Axis

What Is the Gut–Brain Axis?

The gut–brain axis refers to the communication network between:

🧠 The brain

🦠 The gut microbiome

🛡️ The immune system

📡 Hormones

⚡ The nervous system, including the vagus nerve

Communication occurs in both directions.

The brain can influence digestion, gut motility and stress responses, while the gut microbiome produces compounds that may influence immune signalling, nervous system function and overall wellbeing.

Researchers continue to investigate how the gut microbiome may influence:

• Mood and emotional wellbeing

• Stress responses

• Sleep quality

• Cognitive function

• Neurotransmitter pathways

• Inflammatory processes

Importantly, gut health is only one of many factors that may contribute to mental wellbeing.

Perimenopause Is Also a Brain Transition

Perimenopause is often described as a reproductive hormone transition, but it may also be viewed as a neurological transition.

Research suggests fluctuating levels of oestrogen and progesterone may influence:

• Memory

• Learning

• Mood regulation

• Stress resilience

• Sleep quality

• Brain energy metabolism

Oestrogen receptors are found throughout various regions of the brain involved in cognition and emotional processing.

This may help explain why some women report:

✔ Brain fog

✔ Forgetfulness

✔ Reduced concentration

✔ Word-finding difficulties

✔ Mood changes

during perimenopause.

Oestrogen and Neurotransmitters

Research suggests oestrogen may influence several neurotransmitter systems involved in cognition and emotional wellbeing.

These include:

Serotonin

Associated with:

• Mood

• Sleep

• Emotional wellbeing

• Appetite regulation

Acetylcholine

Associated with:

• Learning

• Memory

• Attention

• Focus

Researchers continue to investigate how hormonal changes may influence these pathways during the menopausal transition.

The Tryptophan–Serotonin Pathway

Serotonin is produced from an amino acid called tryptophan, which must come from food.

Foods rich in tryptophan include:

🥚 Eggs

🐟 Fish

🍗 Poultry

🌱 Tofu

🫘 Legumes

🎃 Pumpkin seeds

The conversion of tryptophan into serotonin involves several nutrients, including:

• Vitamin B6

• Magnesium

• Iron

• Folate

• Zinc

A varied and nutrient-dense diet helps provide the nutritional building blocks required for these pathways.

Vitamin B12 and Brain Function

Vitamin B12 is essential for healthy nervous system function.

Low B12 status may be associated with symptoms such as:

• Fatigue

• Brain fog

• Reduced concentration

• Memory difficulties

• Low mood

• Tingling or numbness

Because stomach acid production can decline with age, absorption of vitamin B12 may become less efficient in some individuals.

Discussing B12 testing with your healthcare practitioner may be worthwhile if symptoms are present.

Where the Gut Microbiome Fits In

The gut microbiome is involved in numerous metabolic processes, including pathways related to tryptophan metabolism.

Researchers are increasingly investigating whether the gut microbiome may influence:

• Serotonin pathways

• Immune signalling

• Inflammatory responses

• Stress regulation

• Brain function

Particular interest has focused on short-chain fatty acids (SCFAs) such as:

• Butyrate

• Acetate

• Propionate

These microbial metabolites may contribute to gut barrier integrity, immune regulation and gut–brain communication.

Brain Fog and Memory During Perimenopause

Many women worry that memory changes during perimenopause may indicate something more serious.

Current evidence suggests mild cognitive symptoms can occur during the menopausal transition and may affect:

• Verbal memory

• Learning

• Attention

• Processing speed

• Cognitive flexibility

Importantly, temporary brain fog during perimenopause is not the same as dementia.

Researchers continue to investigate the relationship between hormonal changes, cognition and healthy ageing.

Brain Energy and Metabolic Health

Another emerging area of research involves brain energy metabolism.

Research suggests oestrogen may play a role in how the brain utilises glucose for energy.

Scientists are exploring how changes in hormone levels may influence:

⚡ Brain energy metabolism

⚡ Cognitive performance

⚡ Mental clarity

⚡ Mood

At the same time, factors such as:

• Sleep quality

• Physical activity

• Insulin sensitivity

• Metabolic health

may also influence overall wellbeing and cognitive function.

Nutrients and Compounds Being Investigated in Gut–Brain Axis Research

Researchers continue to investigate the role of various nutrients and compounds in nervous system health and gut–brain communication.

These include:

Magnesium

Found in:

• Pumpkin seeds

• Almonds

• Cashews

• Spinach

• Legumes

Taurine

Found in:

• Fish

• Seafood

• Poultry

• Meat

Vitamin B6

Found in:

• Chicken

• Salmon

• Potatoes

• Bananas

• Chickpeas

Vitamin B12

Found in:

• Fish

• Meat

• Eggs

• Dairy products

Vitamin D

Sources include:

• Sunlight exposure

• Fatty fish

• Eggs

Choline

Found in:

• Eggs

• Liver

• Fish

• Soy foods

Choline is required for the production of acetylcholine, a neurotransmitter involved in learning and memory.

Creatine

Found naturally in:

• Red meat

• Fish

Research is exploring its role in cellular energy metabolism, including brain energy pathways.

N-Acetyl Cysteine (NAC)

NAC is a precursor to glutathione, one of the body's major antioxidants.

Researchers continue to investigate its role in oxidative stress and inflammatory pathways.

Saffron

Emerging research has investigated saffron in relation to mood and emotional wellbeing, although further research is needed.

Probiotics

Specific probiotic strains have been investigated in gut–brain axis research, including:

• Lactobacillus rhamnosus

• Lactobacillus plantarum

• Bifidobacterium longum

• Bifidobacterium infantis

Not all probiotic strains have the same effects and findings remain strain-specific.

Don't Forget the Foundations

While supplements often receive attention, foundational nutrition remains essential.

Prioritise Protein

Protein provides amino acids required for neurotransmitter production.

Increase Plant Diversity

Aim for a variety of:

• Vegetables

• Fruits

• Legumes

• Nuts

• Seeds

• Herbs

• Spices

Include Fibre-Rich Foods

Fibre supports microbial diversity and the production of beneficial microbial metabolites.

Include Omega-3-Rich Foods

Examples include:

🐟 Sardines

🐟 Salmon

🐟 Mackerel

🐟 Herring

Enjoy Colourful Plant Foods

These provide:

• Polyphenols

• Antioxidants

• Fibre

Include Fermented Foods If Tolerated

Examples include:

• Kefir

• Natural yoghurt

• Sauerkraut

• Kimchi

A Gut–Brain Inspired Plate

A nutrient-dense meal could include:

• Grilled salmon

• Mixed leafy greens

• Lentils or chickpeas

• Pumpkin seeds

• Avocado

• Extra virgin olive oil dressing

• Fermented vegetables (if tolerated)

This combination provides:

✔ Protein

✔ Omega-3 fats

✔ Fibre

✔ Magnesium

✔ B vitamins

✔ Polyphenols

✔ Prebiotic fibres

The Gut–Brain–Hormone Connection

One of the most exciting emerging areas of research is the interaction between:

Oestrogen → Gut Microbiome → Brain

Researchers are exploring whether hormonal changes during menopause may influence microbial diversity and microbial metabolites, which may then interact with inflammatory pathways, neurotransmitter systems and brain function.

This does not mean gut microbiome changes cause symptoms such as anxiety, depression or brain fog.

Rather, the gut microbiome may be one of several factors involved in the complex physiological changes experienced during the menopausal transition.

Clinical Takeaway

Perimenopause involves far more than changes in reproductive hormones.

It is also a period of adaptation involving the brain, nervous system, metabolism, immune system and gut microbiome.

Emerging research continues to explore how these interconnected systems may contribute to experiences such as brain fog, mood changes, sleep disturbances and altered stress resilience.

Supporting overall health through nutrition, movement, sleep, stress management and a diverse, fibre-rich diet may contribute to wellbeing during this stage of life.

Disclaimer

This article is for educational purposes only and is not intended to diagnose, treat, cure or prevent any disease. Individual health concerns should be discussed with a qualified healthcare practitioner.

References

1. Cuozzo M, O'Connor C, Power E, et al. Gut-brain communication in menopause: insights into neuroendocrine and microbiome interactions. Proceedings of the Nutrition Society.

2. Nieto MR, et al. Menopausal shift on women's health and microbial niches. Nature Reviews Bioengineering. 2025.

3. Wang H, et al. Gut microbiota has the potential to improve health of menopausal women.

4. Yu X, et al. Mechanism of Microbiota-Gut-Brain in Perimenopausal Mood Disorders.

5. Frontiers in Nutrition. Gut microbiota, menopause and nutritional interventions. 2024.

6. Recent reviews examining menopause, cognition, microbiome interactions and neuroendocrine regulation available through PubMed Central.

7. Cryan JF, O'Riordan KJ, Cowan CSM, et al. The Microbiota-Gut-Brain Axis. Physiological Reviews.

8. Proceedings of the Nutrition Society. Gut-brain communication in menopause: insights into neuroendocrine and microbiome interactions.

9. Briden L. Hormone Repair Manual: Every Woman’s Guide to Healthy Hormones After 40. Pan Macmillan Australia; 2021. Used as a clinical education reference for perimenopause, brain health, mood, sleep and nutrient considerations.