Foods That Strengthen Your Intestinal Barrier: Nutrition Strategies for ME/CFS

For individuals living with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), gut health often plays a key role in symptom management. Recent research has shown that patients with ME/CFS frequently experience increased intestinal permeability—a condition where the lining of the gut becomes more porous, allowing unwanted substances to pass into the bloodstream.

Supporting your intestinal barrier through specific dietary strategies may help reduce inflammation, support immune balance in the gut environment, and improve nutrient absorption. In this post, we’ll explore the science behind intestinal permeability in ME/CFS and highlight foods and nutrients that can help strengthen the gut lining.

"Leaky Gut": Why the Term Is Overused

You’ve likely heard the term "leaky gut" used to describe increased intestinal permeability. While catchy, it’s also a term that gets overused—often to push supplements—without much explanation of the underlying science. It’s a rather dramatic phrase that can give the misleading impression that there are literal holes in your intestinal tract. This simply isn’t the case.

Instead, intestinal permeability refers to how tightly the cells lining your intestines are sealed together by tight junction proteins. When these junctions loosen, small molecules like bacterial endotoxins can pass through more easily. Some permeability is normal, but chronic disruptions can contribute to immune activation and inflammation.

What Is Intestinal Permeability?

Your inner intestine is lined with a single layer of cells, sealed together by tight junction proteins. This barrier plays a critical role in regulating what enters your bloodstream.

Some degree of intestinal permeability is necessary. It allows nutrients, electrolytes, and water to pass from your gut into your body. However, when this permeability becomes excessive or prolonged, larger molecules and bacterial components, such as lipopolysaccharide (LPS), can cross the barrier. This can trigger immune activation and inflammation, contributing to many of the symptoms experienced in ME/CFS.

The Complex Structure of the Intestinal Barrier

It’s easy to picture the intestinal barrier as a thin, delicate membrane—maybe even a single layer of cells separating the inside of the gut from the bloodstream. But in reality, the intestine is a complex, multi-layered structure designed to protect you while still allowing nutrient absorption.

The key component regulating permeability is the single layer of epithelial cells, but this layer is far from unprotected. It is supported by:

1. Tight junctions—specialized proteins sealing the spaces between the epithelial cells, regulating what passes through.

2. A mucus layer—covering the cells, providing a physical barrier to bacteria and large molecules.

3. Immune cells in the gut-associated lymphoid tissue (GALT) – constantly monitoring what gets through and ready to respond to harmful substances.

4. Underlying blood vessels and lymphatic vessels—ready to absorb nutrients but also where bacterial components like LPS can slip into circulation if the barrier is compromised.

When intestinal permeability increases, molecules like LPS from gut bacteria can pass through the loosened tight junctions. These toxins (endotoxin) don’t immediately enter the bloodstream—they first cross into the underlying tissue, where they can be absorbed by:

• Small blood vessels (capillaries) leading to the portal vein and liver.

• Lymphatic vessels, which drain into the lymphatic system and eventually connect to the bloodstream.

This process activates immune responses and can trigger systemic inflammation—something commonly seen in ME/CFS.

Tight Junctions: Your Gut’s Gatekeepers

Tight junctions are protein complexes located between the epithelial cells that line the intestines (and other tissues). Their main role is to seal the space between these cells and regulate the passage of molecules through the space between cells.

Think of your intestinal lining like a brick wall. Each cell is a brick, and the tight junctions are the mortar holding the bricks tightly together. The mortar (tight junctions) ensures that only the right-sized particles (like nutrients) can pass through tiny gaps, while larger, potentially harmful substances are kept out.

How Do Tight Junctions Work?

Tight junctions are passive gatekeepers, meaning they don’t need ATP (cellular energy) to function. Instead, their function depends on assistance from neighboring proteins:

• Structural proteins like claudins, occludin, and zonula occludens (ZO proteins) that form the physical barrier.

• Signaling pathways and cytoskeletal interactions that can dynamically open or tighten the junctions in response to signals like cytokines, stress, or inflammatory mediators.

Research: Compromised Intestinal Permeability in ME/CFS

Several studies have demonstrated that individuals with ME/CFS have increased intestinal permeability. Specifically, research has shown elevated serum levels of immunoglobulins (IgA and IgM) targeting bacterial endotoxin, also known as lipopolysaccharide (LPS). This indicates that LPS—produced by Gram-negative bacteria in the gut—is leaking through the intestinal barrier and triggering an immune response (Maes, 2007).

Key Nutrients and Foods That Support the Intestinal Barrier

1. Zinc

Zinc plays a crucial role in maintaining the structural integrity of tight junctions. Deficiencies in zinc are associated with increased intestinal permeability. Supplementing beyond what is contained in a multivitamin is not recommended, as it may disrupt the balance of key minerals. Instead, focus on zinc-rich foods.

Food sources: Pumpkin seeds, oysters, legumes, beef

2. Glutamine

While glutamine itself doesn’t directly "tighten" the tight junctions, it provides the necessary energy and building blocks for the cells that maintain the barrier. Glutamine-rich foods support the repair and maintenance of intestinal cells, indirectly improving tight junction function and reducing permeability over time.

Several studies show that glutamine can reduce intestinal permeability in specific conditions—like after injury, infection, or stress—by improving epithelial cell health and promoting tight junction protein expression. For example, glutamine supplementation has been shown to upregulate tight junction proteins like claudin-1 and occludin in stressed or damaged gut tissues (Rao, 2012).

Food sources: Chicken, fish, cabbage, spinach

Polyphenols That Improve Intestinal Permeability

Urolithin A: A Postbiotic That Protects Your Gut

One particularly promising compound for intestinal health is urolithin A. It’s not found directly in food but is produced by beneficial gut bacteria when they metabolize certain polyphenols, especially ellagitannins and ellagic acid.

Research shows that urolithin A can improve tight junction function and reduce gut inflammation. Its ability to maintain the integrity of the intestinal barrier is so strong that pharmaceutical companies are now developing drugs that combine urolithin A with NSAIDs. The goal is to reduce NSAID-induced gut permeability and preserve barrier function (Korczak, 2023).

To naturally boost your urolithin A levels, focus on regularly consuming foods rich in its polyphenol precursors:

• Walnuts

• Almonds

• Berries (especially raspberries, strawberries, blueberries)

• Pomegranates

These foods provide the raw materials your gut microbiome needs to produce urolithin A. Supporting a diverse and balanced microbiome further enhances the likelihood of producing this beneficial compound.

Quercetin: Another Polyphenol That Strengthens Tight Junctions

Another polyphenol shown to benefit intestinal barrier function is quercetin. This flavonoid has been demonstrated in research to:

• Upregulate key tight junction proteins such as claudin-4, occludin, and ZO-1.

• Lower inflammation, particularly by reducing pro-inflammatory cytokines like TNF-α and IL-6, which are known to disrupt tight junctions (Uyanga, 2021).

Best food sources of quercetin include:

• Onions (especially red onions)

• Apples

• Berries (such as elderberries and cranberries)

• Kale

• Broccoli

• Green tea

• Capers (one of the highest sources)

Final Thoughts on Strengthening Your Intestinal Barrier in ME/CFS

Focusing on long-term dietary strategies rather than buzzwords like "leaky gut" or over-relying on supplements is key to supporting your intestinal barrier and overall gut health. Prioritizing nutrient-dense foods—such as zinc-rich seeds, glutamine-containing vegetables, and polyphenol-rich foods like walnuts, berries, onions, and apples—gives your body and microbiome the tools they need to maintain tight junction integrity naturally.

References

Maes M, Mihaylova I, Leunis JC. Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syndrome (CFS): indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut-intestinal permeability. J Affect Disord. 2007;99(1-3):237-240. doi:10.1016/j.jad.2006.08.021

Rao R, Samak G. Role of Glutamine in Protection of Intestinal Epithelial Tight Junctions. J Epithel Biol Pharmacol. 2012;5(Suppl 1-M7):47-54. doi:10.2174/1875044301205010047

Korczak M, Roszkowski P, Skowrońska W, et al. Urolithin A conjugation with NSAIDs inhibits its glucuronidation and maintains improvement of Caco-2 monolayers' barrier function. Biomed Pharmacother. 2023;169:115932. doi:10.1016/j.biopha.2023.115932

Uyanga VA, Amevor FK, Liu M, Cui Z, Zhao X, Lin H. Potential Implications of Citrulline and Quercetin on Gut Functioning of Monogastric Animals and Humans: A Comprehensive Review. Nutrients. 2021;13(11):3782. Published 2021 Oct 25. doi:10.3390/nu13113782