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Leaky Gut 101

Leaky Gut 101

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Why intestinal permeability causes so much harm, and what to do about it

Brilliantly packed within the body, the intestinal barrier covers a surface area of over 4,000 square feet and requires about 40% of the body’s energy expenditure. But what happens when it starts to break down?

What is leaky gut?

Hold up your hands and interlace them so the fingers of your left hand slip between the fingers of your right. Wiggle your hands closer together, so there are no visible gaps between your hands. You’ve just created a model of the digestive tract.

What would happen if you poured some beans into the palms of your hands while they were locked together like this? Probably nothing: you’d just have a handful of legumes. But what if you pulled your hands slightly apart, so there were some spaces between your fingers? It would rain beans, your floor would be a mess, and you’d likely become flustered with this learning activity.

Our digestive tracts aren’t all that different, with the cells lining the gut nestled closely together, reinforced by something called tight junctions. The gut serves as a protective barrier, keeping that which we swallow from jumping right into the bloodstream. Good gut integrity prevents water and electrolytes from leaking out of circulation, and blocks toxins and microorganisms from sneaking in. The little “cracks” between the cells, however, allow for the absorption of dietary nutrients that are broken down into very small molecules by digestive enzymes, bile, stomach acid, and the action of the microbes in our gut.[1],[2]

But when the gut lining becomes compromised, the spaces between the cells grow, much like the spaces between our fingers when we pull our hands apart. This describes a state known as increased intestinal permeability – or “leaky gut,” as it’s more commonly called.[3]

And like the storm of beans raining down on the kitchen floor between our “leaky” fingers, trouble ensues when intestinal permeability is compromised. Like the beans between our fingers, bacteria, toxins, undigested food, and other waste can “leak” out of the digestive tract, through the cracks in the gut lining, and into the body. These invaders can then make their way into the bloodstream, triggering the types of immune reactions and inflammation implicated in such conditions as ulcerative colitis, Crohn’s disease, celiac disease, food allergies, irritable bowel syndrome (IBS), and even obesity and cardiovascular disease.[4],[5]

What causes leaky gut, and what can be done to treat it?

Zonulin is an inflammatory protein that helps regulate gut “leakiness” by opening and closing the spaces between cells lining the digestive tract.[6] Altered zonulin expression has been associated with autoimmune diseases, inflammatory conditions, and cancer.[7] Zonulin is upregulated in several autoimmune diseases, and seems to precede their onset, likely contributing to their development.[8],[9],[10],[11],[12] Gastrointestinal infections have also been shown to increase the production of zonulin, accompanied by altered tight junction integrity. Even diet plays a role, with gluten – the protein found in the endosperm of wheat, barley, and rye – being particularly harmful to the gut lining vis-à-vis zonulin expression.[13] Avoiding gluten may therefore be a powerful way to improve intestinal integrity. Digestive aids such as digestive enzymes, pancreatic glandular substances,[14] or supplemental bile[15] may also alleviate the stress on the digestive system by breaking down dietary substances more completely.

Altered zonulin expression has been associated with autoimmune diseases, inflammatory conditions, and cancer.

Infections. Lipopolysaccharide, or LPS, is the major component of the outer membrane of gram-negative bacteria. LPS is also an endotoxin, which, as the name implies, is toxic to us humans. As an endotoxin, LPS activates many types of infection-fighting cells in the human body, creating inflammation and thus harming the gut lining.[16],[17] The body’s reaction to LPS allows the endotoxin to transfer through into circulation, triggering a systemic immune response, creating further inflammation, and taxing the liver and kidneys.[18],[19] This damage contributes to a variety of diseases, including depression,[20] chronic fatigue syndrome,[21] liver disease,[22] heart disease,[23] obesity,[24] and even infertility.[25] Intestinal infections can also degrade intestinal integrity through methods other than the generation of LPS,[26] making natural agents that prevent and treat infections – such as berberine – important in the prevention and management of leaky gut.

Dysbiosis. A shift in the microbial milieu of the gut can alter the ratio of helpful to harmful bacteria. This state, known as dysbiosis, has been implicated with a host of ailments, from obesity to asthma to even depression.[27],[28],[29] Formula-fed babies are also more likely to develop leaky gut later in life than their breastfed peers, in large part due to the positive influences of breast milk on the microbiome.[30] Colostrum, the milk secreted during the first days after a female gives birth, has high levels of many growth factors helpful for the digestive tract, and may therefore be an effective strategy in healing leaky gut.[31],[32] Colostrum also contains lactoferrin, which has broad antimicrobial action and can also be used strategically to bind endotoxin.[33]

In addition to antibiotics, certain medications have also been implicated with dysbiosis and leaky gut. In particular, stomach acid-suppressing medications like proton-pump inhibitors (PPIs)[34] and non-steroidal anti-inflammatory drugs (NSAIDS) have been shown to have adverse effects on the microbiome and gut integrity.[35],[36],[37] The value of a carefully-formulated probiotic supplement in restoring microbial balance thus cannot be overstated, whether in adults, elders, or children. Berberine, the active constituent in Oregon grape root and goldenseal, also improves microbial balance, in addition to reducing intestinal permeability and tonifying motility.[38],[39],[40],[41]

Nutritional Influences. Diets low in fiber[42] and high in saturated fat,[43] sugar,[44] and processed foods[45] all contribute to leaky gut, as does alcohol consumption.[46],[47] Nutritional deficiencies – namely zinc,[48],[49] vitamin A,[50] and vitamin D3[51],[52],[53] – can also lead to increased intestinal permeability. L-glutamine supports the integrity of tight junctions and is the preferred “fuel” for the rapidly-proliferating cells of the intestinal mucosa, which regenerate every 3-5 days.[54] Supplementing these nutrients may therefore improve gut integrity.

Nutritional deficiencies – namely zinc, vitamin A, and vitamin D3 – can also lead to increased intestinal permeability.

Additional agents that support healing of the gut mucosa include slippery elm,[55] N-acetyl-D-glucosamine (NAG), and hydrolyzed collagen. Phosphatidylcholine (PC), a critical component of the protective mucus layer in the gut,[56] and butyrate, an anti-inflammatory short-chain fatty acid produced by healthy bacteria in the gut, also play an important role in healing leaky gut.[57]

Other causes of leaky gut include chronic stress,[58],[59] the aging process,[60] traumas such as burns or injury,[61],[62] inflammation,[63],[64] radiation,[65] and chemotherapy.[66] Strategies to help the body cope with stress, fight inflammation, reverse oxidative stress, and heal from injuries may all therefore be helpful.

Hope for healing

Through a healthy diet, lifestyle modifications, and mindfully chosen natural agents, there is hope for healing leaky gut. By supporting the integrity of the digestive tract, we are better able to protect ourselves against autoimmune disease, allergies, cancer, and host of other ailments. Read on in our second post on this topic to learn more about the nutritional tools that can help resolve leaky gut.


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The information provided is for educational purposes only. Consult your physician or healthcare provider if you have specific questions before instituting any changes in your daily lifestyle including changes in diet, exercise, and supplement use.

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