Leaky Gut and Depression: Testing for Intestinal Barrier Function (SHORT)

You’ve probably heard the phrase “gut feeling,” but what if your gut is actually influencing how you feel?

As a psychiatrist practicing functional medicine, I often see patients with depression or anxiety who also struggle with digestive issues. One hidden factor that links gut and brain health is intestinal permeability—commonly known as “leaky gut.”

Let’s break down what it means, how we test for it, and what you can do to start healing.

What Is Intestinal Permeability—and Why It Matters?

Your gut lining is supposed to act like a selective barrier—letting nutrients through while keeping toxins, bacteria, and undigested food particles out of your bloodstream.

But when that barrier becomes “leaky,” or overly permeable, it can lead to immune activation and inflammation—both in the body and the brain.

Leaky gut has been associated with:

• Chronic inflammation
  
• Autoimmune activity
  
• Nutrient deficiencies
  
• Mood disorders like depression and anxiety

When the gut barrier breaks down, it doesn’t just affect digestion—it can drive brain inflammation, interfere with neurotransmitters like serotonin and dopamine, and even worsen psychiatric symptoms.

How Do We Test for Leaky Gut?

Functional medicine offers several tools to assess the health of your gut lining. The most commonly used tests include:

1. Lactulose/Mannitol Urine Test

This test measures how well your gut barrier absorbs two different sugar molecules:

• Mannitol is small and should pass easily through a healthy gut lining.
  
• Lactulose is larger and shouldn’t pass through unless the gut lining is damaged.

You drink a solution of both sugars and collect your urine over a few hours. Then we analyze how much of each sugar was absorbed.

• High lactulose/mannitol ratio = increased permeability (leaky gut)
  
• Low mannitol alone may suggest villi damage (malabsorption)

2. Zonulin Testing

Zonulin is a protein that regulates tight junctions in your intestinal wall. Elevated levels in stool or blood may indicate your gut lining is letting through substances it shouldn’t.

Studies have linked high zonulin to both gut inflammation and mood disorders, especially when combined with food sensitivities or autoimmune issues.

The Food Sensitivity – Mood Connection

One of the overlooked ways leaky gut contributes to mental health symptoms is through immune reactions to food.

When undigested food particles escape through a leaky gut, the immune system can tag them as threats. This can lead to:

• Food sensitivities (not the same as allergies)
  
• Brain fog, fatigue, irritability
  
• Worsening of anxiety or depression after meals

Food sensitivity testing (like IgG or elimination diets) may help identify hidden triggers that are keeping your gut—and your mood—in distress.

Healing Leaky Gut Naturally: Where to Start

If you test positive for intestinal permeability, the good news is: you can heal it. But it requires a root-cause approach.

Here are the foundational steps I recommend to patients:

1. Remove gut irritants

Start with an anti-inflammatory diet. Avoid ultra-processed foods, refined sugar, gluten, alcohol, and potential food triggers.

2. Repair the gut lining

Support with nutrients like:

• L-glutamine (a fuel source for intestinal cells)
  
• Zinc carnosine
  
• Aloe vera and deglycyrrhizinated licorice (DGL)
  
• Collagen peptides

3. Rebalance the microbiome

Use probiotics, prebiotics, and fermented foods to restore microbial diversity. Address overgrowths like SIBO or yeast if present.

4. Reduce stress

Chronic stress weakens the gut lining. Daily breathwork, therapy, gentle movement, and sleep hygiene are just as critical as supplements.

5. Reintroduce mindfully

Once your gut is more stable, some foods can be reintroduced. This is where personal guidance matters most.

The Bottom Line

If you’re dealing with mood swings, brain fog, fatigue, or persistent depression—and you also have digestive symptoms—your gut barrier may be playing a bigger role than you think.

Testing for intestinal permeability with tools like the lactulose/mannitol test or zonulin levels can uncover hidden inflammation and guide healing from the inside out.

In my integrative psychiatry practice, we treat both the mind and the gut—because real mental health starts with whole-body health.

Want to explore whether leaky gut could be affecting your mental health?
We offer advanced gut testing and root-cause psychiatry to help you find answers.

References

• Fasano, A. (2012). Zonulin and its regulation of intestinal barrier function: The biological door to inflammation, autoimmunity, and cancer. Physiological Reviews, 91(1), 151–175. https://doi.org/10.1152/physrev.00003.2008
• Kelly, J. R., et al. (2015). Breaking down the barriers: The gut microbiome, intestinal permeability and stress-related psychiatric disorders. Frontiers in Cellular Neuroscience, 9, 392. https://doi.org/10.3389/fncel.2015.00392
• Maes, M., et al. (2012). Increased IgA and IgM responses against lipopolysaccharide of enterobacteria in chronic depression: Evidence that gut barrier dysfunction plays a role in depressive disorders. Neuroendocrinology Letters, 33(1), 103–110.