What is Leaky Gut?

When a gastroenterologist or other health professional claims that “a leaky gut does not exist”, I cringe. Their claim is that a leaky gut has no scientific basis.

While “leaky gut” is not a medical problem, it is a FUNCTIONAL problem, that may lead to medical conditions like Crohn’s disease, depression, or other autoimmune disorders down the road.

The claim that leaky gut exists or does not exist is a bias rooted in a health professional’s philosophy, not necessarily science. Research papers often refer to leaky gut as intestinal hyperpermeability and some professionals are not familiar with the discussion or the evidence.

• You can believe that a leaky gut is not a medical concern.
• You can believe that it is overdiagnosed.
• You can also believe that the evidence for a role of a leaky gut in health and disease is not strong enough.

But let’s weigh existence vs. non-existence with a discussion rooted in science. I believe that it is time to replace static thinking of how the gut works, with new recognition of the dynamic roles of the gut in both health and disease.

What is Leaky Gut?

“Leaky gut” refers to a clinical condition of varying severity in which the intestines absorb large, undigested molecules that are normally blocked. The intestines act somewhat like a sieve, keeping most molecules out, and regulating which small molecules are let in. In “leaky gut”, the intestines become hyperpermeable to substances that otherwise have no business being absorbed. Once “leaky gut” or “hyperpermeability” is established, the more important question is to ask “Why?”.

What Causes Leaky Gut?

A leaky gut is thought to be caused by exposure to “toxic” substances or clinical conditions that directly or indirectly damage the integrity of the gut (Bralley, J. 2005). Whether you call it “leaky gut” or “hyperpermeability”, a leaky gut is a functional process by which the intestines fail to regulate what molecules are absorbed into and what molecules are kept out of the bloodstream. This altered control can lead to hypersensitivity responses to food and byproducts of gut bacteria.

Low-grade “endotoxemia” from bacterial overgrowth may lead to autoimmune disorders (1; 2; 3), and the link has been supported by a recent review in February 2012 (4).

Leaky gut is being implicated in a wide range of chronic disease processes & the hypothesis continues to grow in support.

Normal Gut Physiology

“Tight junctions” lie in between the cells of the gut and are largely responsible for maintaining the functional barrier between the intestinal tube contents and the bloodstream. Tight junctions are modulated by a host of physiological & pharmacological factors & their role is much more dynamic than previously recognized  (5). Tight junctions are naturally imperfect. Normally, 1-2% of large proteins pass into the bloodstream & the immune system is able to protect us against foreign and potentially harmful molecules that pass the gut barrier. This is increased when the gut lining is damaged or “leaky” – can be likened to rips in a cheesecloth or large holes in a kitchen strainer.

Up to 70% of the entire immune system is present in the gut in the form of gut-associated lymphoid tissue or GALT. It has a wide range of immune functions including recognizing new threats and equipping immune cells so that they can do their job accurately and efficiently.

Maintaining the integrity of this mucosal immune barrier is increasingly recognized as crucial for health.

Abnormal Gut Physiology

When normal physiology is impaired by exposure to toxic substances, the intestine becomes hyperpermeable to foreign & poorly digested materials. The absorption of these molecules & foreign antigens is capable of initiating an overzealous immune reaction that may reverberate across many body systems.

Common causes of  intestinal hyperpermeability:

• Alcohol (6). A small study of 36 alcoholic patients without liver cirrhosis, malabsorption or malnutrition suggested that small bowel hyperpermeability following alcohol consumption may last at least 4 days and as long as 2 weeks following cessation of drinking (7)
• Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) such as aspirin or ibuprofen
• Viral, bacterial, parasitic, and fungal infections (8; 9; 10; 11; 12).
• High levels of free radicals from bile, food, and drugs (13)
• Inflammatory cell messengers from other disease processes (14; 15)
• Celiac disease, Crohn’s disease, trauma, & burns (16)
• Vaccines (17)
• Food antigens, particularly Gluten and Milk (17)
• Exposure to stress is also well-accepted to disrupt gastrointestinal function (18)
  
• High Fructose Corn Syrup: The Chairman of the Institute for Functional Medicine, Dr. Mark Hyman, MD remarks in The Blood Sugar Solution: “High doses of fructose have been proven to punch holes in the intestinal lining, allowing nasty by-products of toxic gut bacteria and partially digested food proteins to enter your bloodstream and trigger inflammation. Naturally occurring fructose in fruit is part of a complex web of nutrients and fiber and doesn’t exhibit the same biological effects as the high fructose found in corn sugar.“

Implications of Leaky Gut:

Gastrointestinal function plays an essential role in brain function (19). Numerous clinicians and researchers now refer to the links as the “gut-brain axis“. It has been suggested that “leakiness” occurs in the blood-brain-barrier (BBB), and that causes of intestinal hyperpermability may also be associated with hyperpermeability of the BBB.

• For instance, focusing just on serotonin and cortisol imbalance is not sufficient to explain depression. It has been hypothesized that inflammatory and neurodegenerative processes including leaky gut may also predispose an individual to depression (20).
• A possible mechanism is that pro-inflammatory cytokines and lipopolysaccharide from small bowel overgrowth of gram-negative bacteria may “leak” or “translocate” into the bloodstream and induce depressive symptoms (21; 22).
• A 2012 review from the University of Maryland School of Medicine suggests leaky gut may be associated with autoimmune diseases due to the importance of the intestinal barrier in tolerance and immunity to foreign compounds (4).
  • As early as 1997, “leaky gut” has been suggested to play a role in Crohn’s disease – an autoimmune disease of the intestine in response to gluten from wheat, barley & rye. Substances that increase intestinal permeability have been shown to worsen Crohn’s disease, and removal of those substances may put the disease in remission (23)
  • There is evidence that leaky gut has an effect on other pediatric problems such as systemic inflammatory response syndrome (SIRS), inflammatory bowel disease, type 1 diabetes, allergies, asthma, in addition to autism (24)
  • The complex interplay between intestinal bacteria, gut permeability, and mucosal immunity, may create a “perfect storm” for type 1 diabetes (27), an autoimmune disease of the pancreas, and may also play a role in the development of type 2 diabetes (28)
• Problems with intestinal permeability are commonly associated with Autistic children, and there are theories in which gastrointestinal function may influence brain function (17).
• Leaky gut and related oxidative stress may also be a key mechanism involved in Chronic Fatigue Syndrome (25) and there are calls for the development of new drugs aimed at addressing these novel pathways (26).
• Some studies suggest that gastrointestinal health, particularly permeability, may be crucial for heart function and disruptions in the intestinal barrier may stimulate inflammatory reactivity implicated in chronic heart failure patients (29; 30).

Testing for Leaky Gut

There are a number of tests that can suggest or are commonly associated with “leaky gut”. Testing is not always necessary, and the specific choice of testing depends on individual symptoms and health history. In my practice, I am less concerned with identifying a specific “diagnosis”, and more concerned with assessing physiological patterns of function and dysfunction.

1. Presence of bacterial, fungal, viral, & parasitic infections. ex./A microbial ecology stool test can identify certain infections.
2. Adrenal Salivary Index: Acute and chronic stress may suppress immunity and increase susceptibility to mucosal antibody reactions in the gut. Unknown infections or allergic reactions can also drive hidden stress responses and influence the release of other hormones.
3. Secretory IgA (sIgA): Both high and low levels of sIgA (serum, saliva, or fecal testing) can screen for disruptions in mucosal immunity.
4. Antibody testing for Zonulin, Occludin, and Actomyosin which are proteins involved in regulating intestinal permeability. Positive antibodies may suggest intestinal hyperpermeability.
5. Food antibody testing: Common reactive foods are wheat, milk, soy, & corn. Eating foods that you are sensitive to may cause a leaky gut, and likewise, the presence of a leaky gut may cause you to be sensitive to certain foods.
6. Lactulose/Mannitol Intestinal Permeability Challenge Test

• Mannitol and Lactulose are sugars that are not metabolized by the human body and should be excreted in the urine within 6 hours.
  • Lactulose is a naturally large protein only absorbed 1% of the time
  • Mannitol absorption is normally 14%
  • The test looks at the ratio of lactulose/mannitol recovered in the urine. In healthy individuals, the ratio should be <0.03
• The test is performed by swallowing a solution of 5g mannitol and 5g lactulose, collecting urine over 6 hours, assess lactulose and mannitol.
  • If Mannitol is less than 14% absorbed, malabsorption is suspected.
  • If Lactulose absorption was greater than 1%, hyperpermeability or “leaky gut” is suspected.

Natural Approaches for Leaky Gut:

Appropriately address hidden infections and stress imbalance. 4R Program for Gastrointestinal Wellness: Remove offending substances (alcohol, offending foods). Replace digestive enzymes Reinoculate with healthy pre-biotics and probiotics Repair the GI tract with supportive nutrition. It is important to note that each stage of the 4R program may take 30 days or longer.

Additionally, these stages have overlaps with one another and serve simply as a guide to promoting gastrointestinal health. After completion of the repair phase, individuals are encouraged to continue abstaining from offending substances, waiting a period of 6-9+ months before reintroducing them on regular basis. One may also consider rotating mildly reactive foods on a 4-day rotation diet.

It is important to work with a health professional as gastrointestinal health issues can reflect problems in other areas of your health, and so that food allergies are not confused with food sensitivities or intolerances.

Supplements: There are many herbs and supplements that may offer gastrointestinal health benefits. Here is a taste of what appears in the literature…

• A small study suggested that zinc supplementation over two months may improve intestinal permeability in Crohn’s patients (31)
• Glutamine is a favored fuel of colonocytes and certain immune cells and is associated with a protective effect on gastrointestinal integrity.
• Glutamine as well as curcumin from turmeric may modulate the inflammation and oxidative stress associated with hyperpermeability (32)
• Vitamin D levels may have a synergistic role with healthy bacteria in the gut to promote integrity (33)

Reference: Bralley, J. (2005). Laboratory evaluations in molecular medicine: Nutrients, toxicants, and cell regulators. (pp. 223-264). Norcross, GA: Institute for Advances in Molecular Medicine (Affiliate).