Increased Intestinal Permeability (Leaky Gut)

What Is Increased Intestinal Permeability?

[dropcap]I[/dropcap]ncreased intestinal permeability is characterized by dysfunctional intestinal permeability (leakiness) allowing for the penetration of harmful entities from the gut into the bloodstream such as undigested proteins and microbes. The popular name is “leaky gut.”

Q: Why does intestinal permeability increase?

A: Intestinal permeability is an essential function of the small intestinal mucosal lining by which wanted substances such as properly digested foodstuffs are allowed to permeate through the lining to enter the body via the bloodstream and lymphatics. At the same time unwanted substances are kept out.

The mucosal lining is one cell thick and makes up the surface between the digested foodstuffs inside the hollow of the intestine and the underlying tissues.

The mucosal lining is covered by millions of microscopic finger-like structures called villi that project toward the inside of the intestine giving the appearance of a shag rug.

Each one, called a villus, contains a capillary bringing blood to absorb nutrients, a vein to take away nutrients, and a lacteal to absorb and take away digested fat. Its wall is made up of a single layer of tightly connecting cells, called enterocytes.

This single layer of cells separates the contents of our small intestine from the lamina propria (underlying tissues of the small intestine) and the rest of our body. Breaching of this single layer of cells by leakiness can expose lymphocytes (immune cells) located in the lamina propria to a myriad of microorganisms and food antigens, leading to immune reactions.¹

To protect the body from unwanted substances, a gatekeeping barrier system operates to regulate the passage of nutrients, or permeation, through the surface mucosal lining. This system acts to seal the inside body from the gut.

The integrity of intestinal permeability is determined by interactions among several barrier components including the unstirred water layer, mucosal surface hydrophobicity, the surface mucous coat, and cell factors (especially tight junctions).

Tight junctions hold cells tightly together side-by-side to prevent unwanted substances from passing through the lining. Tight junctions are complex structures comprising over 50 proteins, such as the claudin proteins which are considered to be the structural backbone of tight junctions.

Tight junctions include a series of special proteins forming fibrils (springy like proteins) that cross the plasma membrane and interact with proteins in the adjoining cells. Tight junctions are regulated by the protein zonulin.²

If zonulin deregulates from the action of substances such as gliadin (gluten in wheat) and bacteria, the tight junction barrier fails which results in increased intestinal permeability. Dysfunction of the barrier system allows unwanted substances to enter the body where they are damaging to many tissues.

Tight junction dysfunction has been shown to be a part of certain autoimmune diseases such as celiac disease, type I diabetes mellitus, multiple sclerosis, and rheumatoid arthritis. Other diseases associated are cancer, allergies, and infections.³

Important gastrointestinal infections that cause leaky gut include rotavirus, parasites, pathogenic bacteria (escherichia coli, clostridium difficile), and mycotoxins produced by fungi found in stored grain and dried fruit.⁴

Fortunately, the presence of some commensal (friendly intestinal bacteria) and probiotic strains leads to an increase in tight junctions  proteins at the cell boundaries and in some cases prevents or reverses the adverse effects of pathogens, food and stress. Various dietary components are also known to regulate epithelial permeability by modifying expression and localization of  tight junctions proteins.²

What Is Increased Intestinal Permeability In Celiac Disease and/or Gluten Sensitivity?

• Relationship between increased intestinal permeability and celiac disease. Increased intestinal permeability is an associated disorder of celiac disease. Both gastric (stomach) and small intestinal permeability is disrupted in patients with celiac disease.
• Relationship between increased intestinal permeability and epithelium in celiac disease. Each component of the small intestinal barrier system has a different permeability property, but the epithelium (surface cell layer) has been the most intensively studied. Hyperpermeability of this barrier is believed to contribute to the pathogenesis of celiac disease.⁵
• Relationship between increased intestinal permeability and mucosal damage. There is a clear association between degree of mucosal damage and the intestinal permeability ratio, and a normal ratio generally implies near normal small intestinal morphology (cell structure).⁶
• Relationship between increased intestinal permeability and early stage of celiac disease. A study of intestinal permeability showed that the expression of all junction proteins of the small intestinal lining (occludin, claudin 3, zonula occludens 1, and E-cadherin) was already decreased in early stage celiac disease when compared with non-celiac controls, showing leaky gut and confirming earlier studies. Junction protein expression correlated positively with mucosal villus structure and negatively with the number of intraepithelial lymphocytes (IELs), the intensity of small-intestinal autoantibody deposits, and serum autoantibodies. The expression of claudin 3 showed a negative correlation with diarrheal score.⁷
• Relationship between increased intestinal permeability and triggering active celiac disease. Increased intestinal permeability of the mucosal lining could predispose to a high absorption of gluten and exacerbate an existing lesion and hence convert a latent stage of celiac disease to an active enteropathy.⁸
• Relationship between increased intestinal permeability and non-celiac gluten sensitivity. Gluten may also subject the non-celiac patient to gluten sensitivity reactions. Studies have revealed non-gastrointestinal symptoms with positive blood tests for anti-gliadin antibodies without evidence of celiac disease, indicating gluten entering the bloodstream via increased permeability of the small intestine.⁹
• Relationship between increased intestinal permeability and neurologic conditions. Gluten peptides, called gluten exorphine and gliadorphin, mimic the effects of morphine on the brain by the same gut-brain mechanism that allows oral medications used to treat mental problems, such as depression, to enter the brain. People who are unable to break down these peptides may experience mental health problems,¹⁰
• Relationship between increased intestinal permeability and IgA nephropathy. IgA nephropathy, which is an associated disorder in celiac disease, causes increased intestinal permeability (leaky gut) which may predipose the genetically susceptible person to active celiac disease.¹¹
• Relationship between increased intestinal permeability and degree of leakiness. Permeation of disaccharides (double  molecule sugars like sucrose) into the small intestinal lining is by the paracellular route (passing through the spaces between cells)  and thus it correlates with degree of “leakiness” of the intestine. Whereas monosaccharides (single molecule sugars like glucose) are absorbed via the transcellular route (through the cell) so their absorption correlates with mucosal surface area that can absorb. It is important to test gastric and intestinal permeability simultaneously in celiac disease to estimate the sugars rhamose, lactulose, and sucrose in urine.¹²
• Relationship between increased intestinal permeability and timing of testing. Increased intestinal permeability is marked by positivity to a sugar-permeability test. Since timing of the histological response to a gluten free diet is so variable, a sugar-permeability test is an appropriate assessment, particularly within the first 6 months of treatment.⁸,¹³,¹⁴

How Prevalent Is Increased Intestinal Permeability In Celiac Disease and/or Gluten Sensitivity?

Increased intestinal permeability is common in patients with either celiac disease or gluten sensitivity without celiac disease.¹⁵,¹³

What Are The Symptoms Of Increased Intestinal Permeability?

• Increased intestinal permeability is marked by any of these symptoms:

• Gas.
• Bloating.
• Food sensitivities and allergies may develop.

• Other problems that can develop from gluten in the bloodstream: wherever gluten goes, it alarms our immune system to react because it damages any tissue it touches.

• Psychiatric disturbances causing problems like depression and anxiety due to the effects of gluten on the brain.
• Cognitive (thinking) disturbances such as poor attention, judgment and memory or outright confusion due to the effects of gluten on the brain…also called brain fog.
• Behavioral disturbances may include hyperactivity or inappropriate social interaction due to the effects of gluten on the brain.

• When our body surrounds and encloses it, we form granulomas. These hard nodules can develop in the liver, joints, and skin. Granulomas are like pearls formed by an oyster. Our body encapsulates gluten to keep it from hurting our tissues much like an oyster does a grain of sand that lodges inside of it.
• The longer we eat gluten, the greater is our risk of developing other auto-immune disorders such as, alopecia areata (hair loss), psoriasis (skin disorder), Addison’s disease (adrenal gland disorder), Grave’s disease (hyperthyroid disorder) and auto-immune hepatitis (liver disorder). In auto-immune disorders, the development of anti-gliadin antibodies may be attributed to the response to food protein (from gluten) and is often not closely related with celiac disease.

How Does Increased Intestinal Permeability Develop In Celiac Disease and/or Gluten Sensitivity?

• Gluten relaxes the barrier tight junctions between cells that regulate permeability and triggers inflammation by these steps:

1. Gluten that resists complete breakdown into harmless amino acids by normal digestive enzymes yields undigested peptides (small proteins).
2. Undigested peptides induce gut leakiness by relaxing intercellular tight junctions that control spaces between cells lining the small intestines that normally serve as the main barrier to the passage of such large molecules. Undigested peptides then enter into the underlying tissue, the submucosa.

Does Celiac Disease-Related Increased Intestinal Permeability Respond To Gluten Free Diet?

Yes. Intestinal permeability improves within 2 months after starting a gluten free diet.¹⁴

Correcting the factors that cause tight junction disruption and eating a gluten-free diet with foods that have been shown to restore tight junction function after injury, such as these examples:

• Probiotic foods, such as yogurt with live cultures, Kefir, unpasteurized apple cider vinegar, unpasteurized sauerkraut.
• EPA (omega-3 fatty acids) found in fish and some seafood.
• Gamma linolenic acid (omega-6 fatty acids) found in seeds (chia, hemp and flax), walnuts, evening primrose oil, and unrefined canola oil.
• Butyrate  (a short-chain fatty acid) is made in the colon by healthy microbes that live there which is a good reason for eating probiotics and fruits and vegetables because these keep the colon healthy.
• Glutamine (an essential amino acid). Oral glutamine supplementation is shown to prevent an exercise-induced rise in intestinal permeability.¹⁶

6 Steps To Improve Leaky Gut In Celiac Disease and/or Gluten Sensitivity:

• [dropcap]1[/dropcap]Remove the Trigger. Maintain a Strict Gluten Free Diet:

[box type=”shadow” ]Treatment. This condition responds to the complete elimination of gluten, which is the required treatment that improves both leaky gut and gut health.

• Gut health is the foundation to restore ALL health. Restored health will enable you to maintain a strict gluten free diet, just as other life tasks will be easier.
• A strict gluten free diet means removing 100% of wheat, barley, rye and oats from the diet.
• Cutting out bread and other obvious sources of gluten is not good enough for recovery. Even 1/8th teaspoon of flour or bread crumb is enough to sustain the inflammation that is damaging your small intestine, causing increased permeability (leaky gut) and allowing undigested gluten to enter your body where it can damage structures and function, and instigate immune inflammatory responses.

Correct Your Individual Nutritional Needs.

• Eat foods that can replenish missing nutrients. Find them under NUTRIENT DEFICIENCIES.
• Take nutritional supplements as needed. Find them under NUTRIENT DEFICIENCIES.

Recovery. You should begin to feel better within a week and notice more energy as inflammation subsides and the  absorbing cells that make up the surface lining of your small intestine are better able to function.

• Intestinal lining cells are replaced every 5 days. The healing process is like sunburn where the damaged surface layer of skin sloughs off and is replaced with new normal cells.
• Leaky gut normally resolves in two month after starting a gluten free diet and brings about a big improvement in health. Improvement in intestinal permeability precedes morphometric recovery (cell appearance and structure) of the small intestine in celiac disease.⁶
• The intestinal lining may take up to a year to heal.[/box]

• [dropcap]2[/dropcap] Reduce Inflammation. Foods to Eat and Foods Not to Eat:

Because gluten is inflammatory, eliminate OTHER inflammatory foods from your diet to reduce an additive effect to gluten. At the same time, try to eat foods that reduce inflammation (anti-inflammatory).

[box type=”shadow” ]Here Are Major Inflammatory Food Types:

• Damaging Foods. In susceptible persons, includes corn, dairy (cow), and soy. Lactose, the sugar in any animal milk, disrupts intestinal permeability causing leaky gut.⁴
• Allergenic Foods. Includes foods that trigger the immune sytem to produce IgE antibodies. Allergy testing is the usual way to discover these offending foods.
• Shelf Stable Processed Foods. Includes any that contain additives and preservatives. Look for them on the nutrition label of the box or package. Additives and preservatives also disrupt intestinal permeability causing leaky gut.⁴
• Bad Fats. Includes deep fried foods, trans-fats, saturated fats (animal fat/butter), and EXCESSIVE omega-6 fatty acid oils like corn oil. Rancid fats, sodium caprate (a medium chain fat), and sucrose monester fatty acid (a food grade surfactant) induce significant disruption of the intestinal barrier that causes leaky gut.⁴.
• Excessive Refined White Flours (bran layer removed). Includes products made from them such as cookies, bread, cakes, pies. Bran contains the vitamins and minerals that metabolize grains and slows the otherwise rapid entry of sugar from their digestion into the bloodstream. Also disrupt intestinal permeability causing leaky gut.⁴
• Refined Sugars.  Includes white sugar, corn fructose and high fructose corn syrup.
• Certain Spices. Includes paprika and cayenne pepper which disrupt intestinal permeability causing leaky gut.⁴
• Alcohol and Caffeine. Disrupt intestinal permeability causing leaky gut.⁴[/box]

[box type=”shadow” ]Here Are Important Anti-Inflammatory Food Types:

• Fruits Containing Phytochemicals. Includes cherries, grapes, and apples and others.
• Non-Starchy Vegetables. Includes lettuce, kale, onion, broccoli and garlic and others.
• High Quality Complex Carbohydrates. Includes brown rice, quinoa, and root vegetables such as carrots, parsnips, sweet potatoes, turnips, red beets and others. These foods provide needed vitamins and minerals while boosting serotonin levels to help you relax and feel calm.
• Antioxidants. Includes vitamin C-containing foods such as lemon, grapefruit, apricot, Brussels sprouts and strawberries to help us handle stress and reduce irritability. Vitamin E-containing foods such as nuts and seeds. Cocoa is good, too.
• Fish Containing Omega-3 Fatty Acids. Includes tuna, salmon, cod and others.
• Probiotics. Includes fermented foods such as yogurt (sheep, goat), kefir (sheep,goat), saurkraut unpasteurized and unpasteurized apple cider vinegar are very good probiotics, meaning they supply normal microbes needed for colon health and health of the body.
• Prebiotics.   Includes  plant foods with fiber to keep our population of colonic microbes healthy.[/box]

• [dropcap]3[/dropcap] Information Sheet You Can Take to Your Doctor or Other Health Professional:

Click here.

• [dropcap]4[/dropcap] Manage Your Medications Safely: 

[box type=”shadow” ]Certain prescription drugs disrupt intestinal permeability, causing leaky gut. Ask your doctor or pharmacist about this possible adverse effect. Do not stop prescribed medications without supervision.

Here are common offenders but this is not a complete listing.

Antibiotics disrupt intestinal permeabilty and deplete nutrients.

• • Gentomycin, Neomycin, Streptomycin, Cephalosporins, Penicillins deplete B Vitamins, Vitamin K, Probiotics, Vitamin C.
  •  Tetracyclines deplete Coenzyme Q10, Calcium, Magnesium, Iron, Vitamin B6, Zinc, Probiotics, Riboflavin.
  • Cipro depletes Coenzyme Q10, Zinc.
  • Dapsone depletes vitamin K.
  • Penicillins deplete Vitamin B2, Folic Acid, Vitamin B12, Biotin, Vitamin K, Probiotics.¹⁷
  • Erythromycin depletes Vitamin B2, Folic Acid, Vitamin B12, Biotin, Vitamin K, Probiotics.¹⁸

Anti-Inflammatories disrupt intestinal permeability and deplete nutrients.

• • Corticosteroids (Prednisone, Medrol®, Aristocort®, Decadron) deplete Calcium, Vitamin D, Magnesium, Zinc, Vitamin C, Vitamin B6, Vitamin B12, Folic Acid, Selenium, Chromium, Phosphorus.
  • NSAIDS (Motrin®, Aleve®, Advil®, Anaprox®, Dolobid®, Feldene®, Naprosyn® and others) deplete Folic acid.
  • Aspirin and Salicylates deplete Calcium, Folic acid, Vitamin C, Iron, Pantothenate (vitamin B5).

Female hormones disrupt intestinal permeability and deplete nutrients.

• • Oral Contraceptives (Norinyl®, Ortho-Novum®, Triphasil®, and others) deplete Vitamin B2, Vitamin B3, Vitamin B6, Vitamin B12, Vitamin C, Folic Acid, Magnesium, Selenium, Zinc. Correlation analysis shows significant association between some trace elements and the duration of contraception and body mass index of the study participants.¹⁹
  • Oral Estrogen/Hormone Replacement (Evista®, Prempro®, Premarin®, Estratab® and others) deplete Vitamin B2, Vitamin B6, Vitamin B12, Vitamin C, Folic Acid, Magnesium, Zinc.[/box]

• [dropcap]5[/dropcap]Nutritional Supplements To Help Correct Deficiencies:

[box type=”shadow” ]

The type and quantity of nutritional supplements that may be needed depend on which nutrients are deficient.

• Multivitamin/mineral combination that provides 100% once a day is useful to improve overall nutrient levels. This is a safe dose, but always check with your doctor to avoid interactions with medications.
• Calcium citrate is the best absorbed of calcium supplements. Calcium carbonate is a poor choice.
• Vitamin D3 as prescribed following blood test for status.
• Chelated magnesium  as prescribed but do not take at same time as calcium because they compete for absorption.

Storage Note: Store container tightly sealed, away from heat, moisture and direct light to avoid loss of potency. That is, in a safe kitchen cabinet – not in the bathroom or on the kitchen table.[/box]

• [dropcap]6[/dropcap]Manage Natural Remedies: 

[box type=”shadow” ]Hydration:

• Eight glasses of water are recommended per day unless there is a contraindication such as kidney or heart disease. The Institute of Medicine recommends approximately 2.7 liters (91 ounces) of total water, from all beverages and foods, each day for women and 3.7 liters (125 ounces) daily of total water for men.
• If you are thirsty, drink water. Add fresh, squeezed lemon to water. Lemon is anti-inflammatory, alkalizing and provides vitamin C.
• Hydration Test: Urine should be pale yellow. Fingertips should be plump, without pruning but this may not be reliable when fingers are swollen with edema. Lips should be plump, without puckering. The feeling of thirst can be unreliable.
• What is wrong with soda, coffee, tea, and alcohol? These drinks are dehydrating, increase acid, and deplete nutrients.[/box]

[box type=”shadow” ]Carminatives. The following  anti-inflammatory plant sources called carminitives help heal the digestive tract. They also tone the digestive muscles which improves peristalsis, thus aiding in the expulsion of gas from the stomach and intestine to relieve digestive colic and gastric discomfort.

Carminative Food Remedies:

• Raspberry.
• Carrot is also a cleansing digestive tonic.
• Grape is also bile stimulating and a cleansing remedy for sluggish digestion and laxative.
• Redbeets also stimulate and improve digestion and are easily digested.
• Cabbage also stimulates and improves digestion and is also a liver decongestant.
• Lettuce also stimulates and improves digestion and is also an alterative, meaning it improves the function of organs involved with the digestion and excretion of waste products to bring about a gradual change.
• Potatoes are antispasmodic (due to atropine like properties) and a liver remedy.

Carminative Herb Remedies:

• Sage is also a digestive, astringent, bile stimulant and energy tonic that heals the mucosa.  Drink as tea or use in cooking.
• Chamomile, lemon balm, and fennel, (as a tea) also help relieve nervous tension.
• Parsley also relieves indigestion.
• Rosemary as a tea and in cooking also is a nervous system tonic for stress and fatigue, bile stimulant, and can relieve headaches and indigestion. However, because it increases blood sugar levels, it should not be used by persons with insulin resistance or diabetes.
• Thyme is also soothing remedy useful for stimulating digestion of rich, fatty foods.

Carminative Spice Remedies:

• Cloves are also antispasmodic.
• Nutmeg is also useful for indigestion.
• Ginger.[/box]

[box type=”shadow” ]Exercise Helps:

Exercise improves circulation and rids the body of toxins.

• Walking is aerobic exercise that reconditions the whole body to improve stamina. Read more about Exercise and Fitness.
• Weight training builds muscle. Read more about Exercise and Fitness.
• Stretching improves flexibilty. Read more about Exercise and Fitness.

Note: Exercise is important, but the amount and type of exercise undertaken depends on your health. Your first priority is to heal. [/box]

What Do Medical Research Studies Tell About Increased Intestinal Permeability In Celiac Disease and/or Gluten Sensitivity?

RESEARCH STUDY SUMMARIES

“Impaired epithelial integrity in the duodenal mucosa in early stages of celiac disease.” This study investigating whether alterations in epithelial junction protein expression of the small intestinal lining occur already in early stage celiac disease with normal mucosal morphology, and whether this correlates with inflammation indicators and clinical symptoms demonstrated that the mucosal epithelial integrity is disrupted already in early stage celiac disease before the disorder progresses to full-blown enteropathy.

The study involved 10 patients with early stage and 10 patients with overt villus atrophy that were followed yearly according to the study protocol. As controls, 20 non-celiac subjects were included. The expression of junction proteins (occludin, claudin 3, zonula occludens 1, and E-cadherin) was studied in small-intestinal biopsies using immunohistochemistry and Western blot. The correlation between junctional proteins and mucosal morphology, autoantibodies, the number of intraepithelial lymphocytes (IELs), and gastrointestinal symptoms was assessed.

The expression of all junction proteins was already decreased in early stage celiac disease when compared with non-celiac controls. Junction protein expression correlated positively with mucosal villus morphology and negatively with the number of IELs, the intensity of small-intestinal autoantibody deposits, and serum autoantibodies. The expression of claudin 3 showed a negative correlation with diarrheal score (R = -0.314, P = 0.04).⁷

“Celiac disease and HLA DQ in patients with IgA nephropathy.“ This study seeking to establish how common celiac disease is in patients with IgA nephropathy, and whether the possible association can be explained by similiar HLA DQ status demonstrates that although there is no increase in celiac-type HLA DQ, patients with IgA nephropathy carry a risk of developing celiac disease. It can be hypothesized that the increased intestinal permeability in IgA nephropathy may predispose genetically susceptible patients to celiac disease.²⁰

“Improvement in intestinal permeability precedes morphometric recovery of the small intestine in coeliac disease.” This study comparing changes in intestinal permeability (lactulose/rhamose absorption as an indicator of microvilli recovery) with changes in intestinal biopsy (villus area, crypt length, and mitotic count per crypt) at diagnosis and various intervals after commencing a Gluten Free Diet to assess small bowel recovery in adults with Celiac Disease demonstrated that intestinal permeability improves within 2 months after starting a Gluten Free Diet, but measurable intestinal biopsy improvement requires ingestion of a Gluten Free Diet for at least 3-6 months, and even then remains incomplete.¹⁴

Sources:

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