Reviewed by Romilly Hodges (October 2020)
Leaky gut is often written and talked about as a black and white concept: Either you have it or you don’t. And if you have it, you’ll want to ‘heal’ it. While this is true to some extent – after all, health begins in the gut, and we know increased gut permeability is a factor in many different chronic conditions – it doesn’t tell the whole story. For instance – did you know that your gut goes through different levels of permeability even throughout one day? And that not all permeability is pathological?
In this article, you’ll find an explanation of some of these nuances, and (we think) the most exhaustive list you’ll have come across of factors that either promote leakiness or reduce it. Importantly, you’ll see that we can have some degree of ‘normal’ leakiness that isn’t always problematic. And you’ll be armed with a good reference list of factors to watch out for or lean on if you’re working with a problematic leaky gut.
I originally researched and wrote the (popular) first version of this article several years ago, but thanks to Jessica Kovalchik CNSc and Josette Herdell CNS, it’s now updated with even more recent research on factors that increase or decrease permeability. And it continues to be a fantastic resource.
Enjoy! – Romilly Hodges CNS IFMCP, Nutrition Programs Director
What is a Leaky Gut?
Leaky gut, also known by its scientific name intestinal hyperpermeability, is a term you commonly hear in the functional medicine world. And with good cause as it is an underlying contributor to a wide array of symptoms and diseases.
The intestinal barrier is an incredibly thin entity—just a single layer of epithelial cells separates the intestinal lumen from the underlying tissue. These cells are primarily absorptive enterocytes, but also consist of specialized cells with secretive, hormonal and immune functions. All these cells are held together by protein-based junctions that play a crucial role in regulating what is allowed to cross the intestinal barrier.
Various signaling pathways alter the function and expression of these proteins leading to either increased or decreased barrier permeability. For instance, gliadin, a type of protein in wheat and other grains, causes the release of zonulin and loss of junction integrity, even in non-celiac, non-gluten-sensitive individuals. Perhaps small amounts of gluten in a non-sensitive person with an otherwise healthy gut isn’t a big concern (although it’s all-too-easy to end up with bagel for breakfast, sandwich for lunch and pasta dinner, all of which adds up to rather too much gluten!). But for other people, it can tip them into a problematic range of leakiness.
What’s the problem with a leaky gut? Leaky gut has been associated with a rage of chronic symptoms and diseases. Here are just some:
Abdominal distention (A)
Abdominal pain (H)
Acne (H)
Allergies (R)
Amyotrophic lateral sclerosis (R)
Ankylosing spondylitis (A)
Autoimmune disease (H, A)
Brain fog (R)
Celiac disease (H)
Crohn’s disease (R)
Constipation (H)
Depression (H)
Diabetes-type 2 (H)
Diarrhea (H)
Dysbiosis (A, H)
Eczema (H)
Elevated histamine (H)
Fatigue (R)
Food intolerance (H)
Gastroenteritis (H)
Hives (H)
Hypochlorhydria (H)
Irritable bowel syndrome (H)
Inflammation (H, V, V, V)
Inflammatory bowel disease (A, H)
Migraine headaches (R)
Non-alcoholic fatty liver disease (H)
Obesity (independent of diet) (A)
Obstructive jaundice (H)
Obstructive sleep apnea (H)
Psoriasis (H)
Rosacea (H)
SIBO (H)
Ulcerative colitis (H)
Yeast (candida) (V)
A Barrier in Flux
We have to recognize that intestinal permeability is naturally dynamic and that ‘leakiness’ is rather more a daily sliding scale that is always changing depending on external inputs and internal factors. We want these fluctuations to be in a healthy range, not in a pathological range.
In today’s environment, our gut is continually exposed to substances that undermine its integrity. Pesticides, food additives, excess sugar, NSAIDs and antibiotics are just some of the culprits in promoting the loss of healthy barrier function. If there is significant gut damage, fluctuations may not be getting into a healthy, regulated range at all, and that needs our attention. Even a transient shift towards increased permeability in someone who, say, has an autoimmune condition, might exacerbate the underlying disease pathophysiology. Considering gluten avoidance makes sense in those circumstances.
The Latest Research on Intestinal Barrier Modulators
Did you know that many factors influence permeability, including specific food bioactive compounds, hormones, microbes, antigens, additives, pesticides, mold, and lifestyle practices? Below we have compiled an extensive list of factors that have been shown to affect intestinal permeability.
As we’ve argued, not all factors that increase permeability should be automatically considered pathological in every situation. However, where you recognize you’re having a significant exposure and you suspect leaky gut, it can be useful to take extra care to avoid these when working to restore a healthy level of gut integrity.
Of course, this is a work-in-progress as the research in this area only continues to come forth. This list, originally published in 2016, is now updated with additional research.
Factors that INCREASE intestinal permeability
Be careful with your exposure to these, especially if you have a chronic condition.
References (A: animal study; H: human study; R: review; V: in vitro)
DIET & BOTANICALS
- Alcohol (V)
- Fast foods and processed foods (H)
- Food additives (A, H)
- Food allergies (R, H)
- Gliadin (gluten) (R)
- Lectins (A, V)
- Saccharin (A, V)
- Sugar (H)
- Ascorbic acid (vitamin C) (H) – see also ‘factors that decrease…’
- Zinc deficiency (A, H)
- Capsianoside (paprika, Cayenne, peppers) (V)
- Genistein (soy, non-fermented) (A, A)
- Senna (V)
LIFESTYLE
- High intensity exercise (H, H)
- Night shift work (coupled with alcohol) (H)
- Stress (including subacute/chronic) (A, A, A, A, A)
- Concussion (A)
- Elevated cortisol (H)
ENVIRONMENTAL
- Arsenic (A)
- Acrolein (a dietary and environmental pollutant) (V)
- Bisphenol-A (BPA) (A)
- Chlorpyrifos (pesticide) (A)
- Glyphosate (pesticide) (V)
- Klebsiella oxytoca bacteria (V)
- Mercury in food (V)
- Mycotoxins
- Parasitic infection (V)
- Polychlorinated biphenols (PCBs) (V)
- Titanium dioxide in food (V)
MEDICATIONS
Factors that DECREASE Intestinal Permeability
DIET & BOTANICALS
- Agaricus mushroom (selenium enriched) (A)
- Aloe (V)
- Amino acids (R)
- Andrographis (V)
- Anthocyanins (a flavonoid that gives foods red, purple, blue colors) (V, 2019)
- Antioxidant polyphenols (chicory) (V)
- Apple polysaccharides (A)
- Astragaloside IV (from Astragalus membranaceus root) (A)
- Arginine (V)
- Berberine (A)
- Boswellia serrata (Frankincense) (V)
- Butyrate (ghee, prebiotics) (A, A, A, A)
- Calcium (A)
- Casein (A)
- Chitosan (type of fiber) (V)
- Cinnamomum japonicum Cinnamon (V)
- Citrulline (A)
- Colostrum (H, H, A)
- Conjugated linoleic acid (omega-6 fatty acid) (A)
- Cruciferous vegetables (A)
- Curcumin (turmeric) (A, A)
- Dihomo-γ-linolenic acid (omega-6 fatty acid) (V)
- Docosahexaenoic acid (omega-3 fatty acid) (A)
- EGCG (green tea) (V)
- Eicosapentaenoic acid (omega-3 fatty acid) (A)
- Fermented foods (V)
- Flavonoids (quercetin) (V)
- Folate (H)
- Fiber (R, A)
- Fruits (R)
- Garlic (A)
- Ginger (A)
- Ginkgo biloba (A)
- Ginseng (Panax ginseng) oligopeptides (GOP) (A)
- Glutamine (H, R)
- Glycine (V)
- Grape seed extract (A)
- Hesperidin (V)
- Laminaria japonica extract (edible brown seaweed) (V)
- Lactoferrin (in breast milk) (V)
- Licorice (DGL) (V)
- Lipoic acid (A)
- Marshmallow (H)
- Moxibustion (dried mugwort) (A)
- Naringenin (citrus) (A)
- N-acetyl cysteine (NAC) (A)
- Oats (A)
- Olive oil (A)
- Oregano (A)
- Phosphatidylcholine (V)
- Polysaccharides (rhamnogalacturonan) (V)
- Prebiotic galacto-oligosaccharides (GOS & BMO – Bovine milk oligosaccharides) (A, A)
- Psyllium fiber (A)
- Quercetin (apples, onion, parsley, and many more plant foods) (R)
- Resveratrol (V, A)
- Rhubarb (H)
- Selenium (A, A, A)
- Sinensetin (found in citrus peel) (V)
- Slippery elm (H)
- Spirulina (A)
- Thymol (thyme) (A)
- Triphala (A)
- Tryptophan (H)
- Vanillin (vanilla) (A)
- Vitamin A (as retinoic acid) (H, V)
- Vitamin C (H) – see also ‘factors that increase…’
- Vitamin D (H, V, V)
- Vitamin E (A, A)
- Whey (A, A, A)
- Zinc carnosine (H, V)
LIFESTYLE
- Avoidance of toxins (inferred)
- Judicious use of pharmaceuticals (avoidance where possible, inferred)
- Moderate exercise (inferred)
- Regular sleep/circadian cycles (inferred)
- Stress management (inferred)
REGULATORY SUFFICIENCY
ENVIRONMENTAL
- Akkermansia (A)
- Bifidobacterium animalis (A)
- Bifidobacterium infantis (V)
- Bifidobacterium lactis (H, V)
- Bifidobacterium longum (H)
- Clostridium tyrobutyricum (V)
- Eschericia coli Nissle (not to be confused with pathological E. coli strains) (V)
- Lactobacillus acidophilus (H, V)
- Lactobacillus bulgaricus (H)
- Lactobacillus plantarum (H)
- Lactobacillus reuteri (H)
- Lactobacillus rhamnosus (H)
- Saccharomyces boulardii (H)
- Streptococcus thermophilus (V)
MEDICATIONS
So, here’s the key… we don’t always need to avoid all factor that increase permeability. However, if we suspect leaky gut, we might avoid some of these for a period of time. Learn more about the functional medicine approach to healing the gut and strengthening intestinal epithelium in our blog Our “6R” Gut Program: Six Steps to Save Your Health Through Your Gut.