The Gut-Brain Axis: The Hidden Root of Depression?

Have we been looking at depression through the wrong lens?

For decades, the dominant narrative has been a “chemical imbalance” in the brain — serotonin deficits, dopamine dysfunction, and a quick-fix pill to “correct” it.

But what if the root cause lies far below the brain?

Deep in your gut.

Your gut is home to over 100 trillion microbes — more than ten times the number of human cells in your body.

These microbes aren’t just innocent bystanders.

They produce neurotransmitters like serotonin, GABA, dopamine, and norepinephrine — all critical for mood regulation.

They also modulate inflammation, shape your immune system, and influence the development of your brain — starting in the womb.

This bidirectional communication network between the gut and brain is called the gut-brain axis, and it’s rewriting everything we thought we knew about mental health.

Chronic low-grade inflammation is now recognised as a major driver of depression.

And the gut is often the source.

Disruptions in gut microbial balance (called dysbiosis) can lead to increased intestinal permeability — aka “leaky gut”.

This allows bacterial fragments like lipopolysaccharide (LPS) to escape into the bloodstream, triggering a full-body immune response.

That includes inflammatory cytokines like IL-6 and TNF-α, which are known to induce depressive symptoms.

This isn’t hypothetical. It’s backed by clinical evidence, animal models, and biological plausibility.

Certain strains of bacteria — including Bifidobacterium infantis, Lactobacillus rhamnosus, and Lactobacillus helveticus — have been shown in studies to reduce anxiety and depressive behaviour.

They’ve been dubbed psychobiotics.

These microbes can:

• Lower cortisol and reduce HPA axis overactivation
   
• Modulate cytokines like IL-10 (anti-inflammatory)
   
• Improve tryptophan availability for serotonin production
   
• Influence brain-derived neurotrophic factor (BDNF), which supports neuroplasticity
   

In one double-blind human study, subjects taking probiotics showed improved mood, reduced perceived stress, and lower cortisol levels — all without a single pharmaceutical.

The “hygiene hypothesis” suggests that our ultra-sanitised, antibiotic-rich, and nature-deprived modern lives are stripping us of essential microbial exposures.

The updated “old friends” hypothesis goes further — we co-evolved with beneficial microbes that we now lack.

The rise in depression, anxiety, autism, and autoimmune conditions isn’t a coincidence.

It’s ecological collapse. In the gut.

Depression is not just in your head.

It’s in your gut. Your immune system. Your diet. Your lifestyle.

That's why so many people with Crohn's disease or Ulcerative Colitis also have problems with depression or anxiety during flares, or even when gut symptoms are less active. 

Treating the brain in isolation is like blaming the smoke while ignoring the fire.

Evrensel, A., & Ceylan, M. E. (2015). The Gut-Brain Axis: The Missing Link in Depression. Clinical Psychopharmacology and Neuroscience, 13(3), 239–244. https://doi.org/10.9758/cpn.2015.13.3.239