The Gut-Brain Depression Axis: How Dysbiosis Inflames Your Brain

You’ve probably heard that low serotonin causes depression. You may even be on an SSRI (selective serotonin reuptake inhibitor) to increase serotonin in your brain. But here's what most doctors don't tell you: your gut is central to how well your brain can make and regulate serotonin.

Here's how it works: about 90% of your body's serotonin is produced in your gut—but that serotonin doesn't travel to your brain. It stays in your gut and peripheral tissues, regulating digestion, immune function, and signalling. Your brain makes its own serotonin from tryptophan (an amino acid from protein).

So why does gut health matter for brain serotonin and mood?

When your gut microbiome is healthy and diverse, it:

• Produces beneficial compounds like short-chain fatty acids (SCFAs) that reduce inflammation and support neurotransmitter production

• Regulates how much tryptophan (serotonin's building block) gets to your brain

• Communicates directly with your brain via the vagus nerve, signalling whether you're safe and well-nourished—or inflamed and under threat

• Keeps systemic inflammation low, so your brain can efficiently make and use serotonin

When your gut is dysbiotic (imbalanced) or inflamed, all these processes break down, and your brain struggles to produce the serotonin your antidepressant is trying to work with.

This is why many women stay depressed despite SSRIs: the medication is trying to make serotonin work better in the brain, but if your gut is dysbiotic and inflamed, your brain can't produce or use serotonin effectively—so the drug has nothing to work with.

The Gut-Brain Axis: A Two-Way Communication System

Your gut and brain are in constant communication through multiple pathways:

The Vagus Nerve Highway

The vagus nerve is a major nerve that directly connects your gut to your brain. Signals travel both directions:

• Gut → Brain: Your gut sends signals about inflammation, nutrient status, bacterial populations to your brain

• Brain → Gut: Your brain sends signals that affect digestion, barrier integrity, and bacterial composition

When your gut is dysbiotic and inflamed, it sends inflammatory signals up the vagus nerve to your brain. Your brain interprets these signals as "something is wrong," triggering depression, anxiety, and brain fog.

Bacterial Metabolites

Your gut bacteria produce compounds called metabolites—particularly short-chain fatty acids (butyrate, propionate, acetate). These metabolites:

• Nourish your gut barrier and brain tissue

• Regulate inflammation

• Support neurotransmitter production

• Strengthen the blood-brain barrier

A healthy microbiome produces abundant metabolites. A dysbiotic microbiome produces minimal metabolites. Without them, your brain becomes inflamed and depressed.

Lipopolysaccharides (LPS) & Bacterial Toxins

When your gut barrier is compromised, bacterial toxins (particularly LPS from gram-negative bacteria) leak into your bloodstream. These toxins are recognized as threats by your immune system, triggering systemic and neuroinflammation.

Neuroinflammation is the biochemical basis of depression. An inflamed brain produces depression.

The Oestrogen Metabolism Connection

Your gut bacteria help break down and recirculate oestrogen through what's called the estrobolome. When dysbiosis occurs:

• Oestrogen can't be properly metabolized

• Excess oestrogen backs up

• Dysregulated oestrogen dysregulates neurotransmitters

• Depression and mood swings worsen

This is particularly relevant for midlife women whose oestrogen is already dysregulated.

Why Midlife Women Develop Dysbiosis

Decades of Antibiotic Use

Every course of antibiotics kills both harmful and beneficial bacteria. By midlife, if you've taken multiple antibiotics (for infections, acne, UTIs, etc.), your microbiome has been repeatedly decimated. The beneficial bacteria often never fully return.

Low-Fibre Diet

Your gut bacteria feed on fibre. If you've been on restrictive diets throughout your life (common for midlife women due to diet culture), you've been starving your beneficial bacteria.

Stress & Cortisol

Chronic high cortisol (see 'Cortisol Dysregulation and Depression: How Chronic Stress Rewires Your Brain') damages the gut barrier and kills beneficial bacteria while promoting pathogenic bacteria growth. Stress literally dysbioses your gut.

Perimenopause Hormonal Shifts

The decline of oestrogen during perimenopause affects the estrobolome (oestrogen-metabolizing bacterial community). This dysbiosis further impairs oestrogen metabolism and worsens depression.

Poor Diet Quality

Ultra-processed foods feed pathogenic bacteria and starve beneficial bacteria. Vegetable oil and refined carbs promote dysbiosis. A typical Western diet creates dysbiosis within weeks.

Toxin Exposure

Heavy metals, pesticides, and mould toxins damage the gut barrier and kill beneficial bacteria.

NSAID & Medication Use

Non-steroidal anti-inflammatories (ibuprofen, naproxen) and other medications damage the gut barrier and create dysbiosis in the microbiome.

How to Recognize Gut Dysbiosis

GI symptoms:

• Bloating or gas

• Constipation or diarrhoea

• Irregular bowel movements

• Food sensitivities or intolerances

• Leaky gut symptoms (see below)

• Chronic gas or digestive discomfort

• Difficulty gaining satiety

`'Leaky Gut`' symptoms (compromised intestinal barrier):

• Food sensitivities that seem to develop overnight

• Systemic inflammation (widespread pain, swelling)

• Brain fog

• Fatigue

• Mood dysregulation (anxiety, depression, irritability)

Mood & brain symptoms:

• Depression

• Anxiety

• Brain fog

• Difficulty concentrating

• Memory problems

• Mood swings

Immune symptoms:

• Frequent infections

• Autoimmune symptoms

• Unexplained inflammation

• Skin problems (acne, rosacea, eczema)

Systemic symptoms:

• Unexplained weight gain or difficulty losing weight

• Fatigue

• Joint pain

• Hormone dysregulation

All of these can stem from dysbiosis and leaky gut.

The Bottom Line

Your depression may not be a serotonin problem requiring medication. It may be a dysbiotic gut that's stopped producing serotonin and is inflaming your brain instead.

The good news? Gut dysbiosis is highly responsive to dietary change, probiotic support, and lifestyle modification. Within 6-8 weeks of consistent intervention, most people notice significant mood improvement.

Your gut is asking for help. Listen.

Next: We explore progesterone and oestrogen balance—and why hormone imbalance during midlife is such a powerful driver of depression.

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If you've been struggling with your digestive health for some time and suspect your gut might be affecting your mood, energy, or overall wellbeing, find out how we can help on our Gut Health page.

Reference Research:

- Nature Reviews Neuroscience - "The Gut Microbiome and Mental Health"

- Psychosomatic Medicine - vagus nerve signaling and depression

- Trends in Molecular Medicine - the gut-brain axis in mood disorders

- NCBI/PMC - "Dysbiosis and Depression" meta-analysis

- Journal of Psychiatry and Neuroscience - psychobiotics and depression treatment

- Frontiers in Immunology - dysbiosis and neuroinflammation