December 2025

Depression

• Beyond a mood disorder
• It’s not just in your brain
• The Gut Brain Axis
• Herbal Support For Depression

When we think about the gut, the first thing to come to mind is digestion. However, the gut is connected to the brain and affects cognition and mood.

Depression: The Gut Brain Axis

The autonomic nervous system

The autonomic nervous system is the branch of the nervous system that manages your survival. It is a complex tightrope dance that regulates heart rate, blood pressure, breathing, metabolism, and fluid balance.

It is a flexible system that has developed two functional modes of operation. The sympathetic nervous system is your stress response, and the parasympathetic nervous system is your rest, digest, and relax response.

The HPA axis

The HPA axis is your stress response, activated whenever you challenge yourself. When the body feels challenged, it will rise and recruit all its resources to survive. Usually, that means more blood to the heart, lungs, and muscles so you can fight or flee.

Stress also means less blood, rich in nutrients and oxygen, is directed into the gut, leading to subpar digestion and absorption, and nutrient deficiencies that increase stress, inflammation, and depression.

The relax and digest response

The vagus nerve is the longest cranial nerve in the body. It connects the brain stem to the heart, lungs, stomach, liver, and digestive tract.

The vagus nerve plays a vital role in the parasympathetic nervous system, your rest and digest response, making it a major neural pathway for information between your gut and your brain. Information flows both ways: stress affects your digestion and absorption, and gut conditions affect your cognition and mood.

Although the vagus nerve can directly sample gut contents, it senses gut information through enteroendocrine cells that control gut motility, secretion, inflammatory responses, and mucosal defense.

Vagus nerve pathways regulate inflammation by releasing the neurotransmitter acetylcholine, which binds to immune cells and inhibits the production of proinflammatory immune mediators.

Chronic sympathetic activation (fight-or-flight) impairs the body’s natural anti-inflammatory regulation. When we’re stuck in defensive nervous system states, the vagus nerve becomes less active, reducing this natural anti-inflammatory regulation.

Immune signaling

70-80% of the immune system lives in the gut. Gut conditions, such as leaky gut and dysbiosis, increase the release of proinflammatory cytokines (immune messengers) that travel through the blood to the brain and can promote brain fog, memory loss, depression, and anxiety.

The gut epithelium is a single cell layer that serves as both a selective barrier and an active immune surveillance system. 

As a barrier, the epithelium blocks toxins, allergens, and pathogens that move through the gut lumen from diffusing into the body. Barrier disruption and diffusion of toxic substances induce mucosal inflammation and tissue damage, which play a crucial role in IBD, IBS, and celiac disease.

The epithelium is not a passive barrier; instead, it “tastes” the contents of the lumen, evaluates them, and responds to allergens and pathogens by recruiting immune cells.

Proinflammatory immune cells released in the gut travel through the blood to the brain, activating microglia, brain immune cells, leading to brain inflammation that alters mood and cognition.

The microbiome

Research suggests that an imbalance of the microbiota-gut-brain axis may play a vital role in depression. Therefore, restoring the gut-brain microbiome balance can alleviate depressive symptoms. 

The microbiome is a diverse ecology of bacteria that lives in your colon. There are 10 bacterial cells in your colon for each human cell in your body. Genetically, you are much more similar to any human on this planet; however, your gut microbiome composition is unique to you.

Gut bacteria are not a passive “renter” in the gut: instead, they ferment fiber, produce short-chain fatty acids, synthesize vitamins, and support a robust immune system.

Short chain fatty acids produced by gut bacteria have a protective effect on the brain. They support the integrity of the blood brain barrier, a specialized endothelial tissue that protects the brain from pathogens and large molecules. These short chain fatty acids can cross the blood-brain barrier and directly influence brain function. They reduce neuroinflammation by inhibiting microglial activation and influencing the stress response.

Another fascinating effect of short chain fatty acids, specifically butyrate, is the release of anti-inflammatory compounds that modulate the immune system both locally and systemically.

Gut bacteria produce 70% of the overall serotonin produced in the body. The serotonin produced in the gut cannot cross the BBB and primarily regulates gut motility. Nevertheless, serotonin produced in the gut does communicate with the brain.

Why is it important?

When we look at the root cause of depression, all the fingers point to inflammation. In my last post, Depression – It’s not just in your brain, I described how the typical Western lifestyle promotes inflammation, wreaking havoc on our nervous system.

One of the core principles of preventing and reversing depression is an anti-inflammatory diet.

What does it look like?

Let’s start by adding:

• 1/2 lb wild-caught cold water fish for the omega-3 fatty acids. Omega-3 is a substrate for anti-inflammatory immune messengers.
• Fiber and resistant starch are the raw materials that gut microbes ferment to produce short-chain fatty acids.
• Polyphenols are found in berries, pemogrants, and olives. The bacteria metabolize these polyphenols into compounds that then circulate and help modulate inflammation throughout the body.

Eliminate:

• Processed foods
• Simple carbs and sugars

They feed strains of bacteria that release proinflammatory compounds.

People don’t become depressed because of an SSRI deficiency. Only a third of the people with depression benefit from SSRIs.  

Beyond popping a pill, depression is a lifestyle condition. Therefore, reversing depression should start with the basics: diet, stress, and sleep. Meds and herbs can support you on your healing journey and give you the energy and motivation to do the work.