The Many Causes of Leaky Gut Syndrome

Last time we introduced the concept of leaky gut syndrome and discussed how the gut works. By now it should be clear that there are a lot of things that go on every minute of every day to ensure normal gut function- your microbes are talking to each other, your immune system is surveying the scene, and your intestinal lining is continually renewing itself. But what happens when one or more things interfere with normal gut function? Gut health is multifaceted it is no surprise that there are numerous things that can increase intestinal permeability (4). The easy way to explain this is that anything that causes inflammation of any kind is going to have an inflammatory effect on the gut... but let's explore a few mechanisms.

•  Anti-biotic drugs (and herbs) don't just kill the bugs you want to kill- they kill whoever is susceptible to them. Unfortunately, this often includes the "good" microbes that keep your gut healthy. While this may be the least of your concerns if you are on the brink of death from sepsis, it is something to consider when dealing with relatively common ailments such as UTIs, ear infections, and sinus infections. Before you walk out of your doctors office with that anti-biotic script ask yourself "would I be able to shake this bug without this drug?" and "what other effects will this drug have on me?" In my experience, ear infections are almost always viral and thus unresponsive to anti-biotics, UTIs can be killed very quickly with lots of water and some uva ursi, and sinus infections will go away good ol fashioned rest and neti-pot washes.
• NSAID drugs (non-steroidal anti-inflammatory drugs) such as ibuprofen and advil are notorious for causing stomach ulcers, so it's not a surprise that they damage the rest of the gut lining in the same way. There are multiple mechanisms at play here, including direct irritation of the GI lining by the drug when it is ingested, uncoupling of mitochondrial oxidative phosphorylation, and the inhibition of COX 1 and 2 (1). That last part is especially important. The Cyclooxygenase enzymes aka COX 1 and COX 2 are enzymes responsible for the formation of prostaglandins, or local cellular messengers. NSAIDs are said to be "non-selective COX inhibitors" because they block both enzymes. The sad news is that while blocking COX 2 gets rid of your pain and reduces inflammation, COX 1 is a good guy we really don't want to block. COX 1 is responsible for the formation of anti-inflammatory prostaglandins and actually helps maintain the gut lining. Whoops!
• Food intolerances are becoming all the more common, the two most common being to gluten and dairy. Exposure to gluten is one of the most potent triggers for zonulin release from the gut lining (which goes hand in hand with increased permeability) even in people without Celiac disease (2).
• Head injury has been shown to release zonulin, the same molecule that is released from the GI tract when it is injured. This tight junction protein not only closes the gap between epithelial cells in the GI tract, but it plays the same role in maintaining the blood-brain-barrier. When traumatic brain injury was applied to a rodent model in the laboratory setting Santos and colleagues found "significant damages to gut structure and impairment of barrier function" only three hours after injury (3). The authors believe that when zonulin is released from the injured blood-brain-barrier it makes its way to gut via the blood and signals the gut lining to become more permeable, too.
• Gastrointestinal infections
• Chronic stress
• Enviromental toxins
• Chemotherapy and radiation therapy
• Autoimmune disease
• Alcohol
• Corticosteroids
• Excessive sugar consumption

With so many things that cause leaky gut syndrome in the world it's a wonder why we don't all have leaky guts. Keep in mind that there are surely other things that cause the gut barrier to break down, but this is a good starter list. Also, people's reactions to the inflammatory stimuli can be much different. For some, stress may be what sends them into a diarrhea-ey downward spiral, for others it may be NSAID use. Everybody has different capacities to handle inflammation based on variations in dietary antioxidant consumption and their body's ability to make its own antioxidants. Either way, I look at this list and am reminded of why I have to eat as clean as humanly possible- you never know what inflammatory thing will try to take you down next!

In health,

Nikki


References:
(1) http://farncombe.mcmaster.ca/document/WallaceBestPractResClinGastroenterol2000141147-159.pdf

(2) Fasano Alessio, Zonulin and Its Regulation of Intestinal Barrier Function: The Biological Door to Inflammation, Autoimmunity, and Cancer, Physiol Rev 2011; 91: 151–175.

(3) Santos Alejandro, Intestinal Permeability to Glucose after Experimental Traumatic Brain Injury: Effect of Gadopentetate Dimeglumine Administration, Nordic Pharmacological Society Basic & Clinical Pharmacology & Toxicology 2008, 103, 247–254.

(4) The Textbook of Functional Medicine 2010 pg 192

(5) Lipski, Elizabeth, Leaky Gut Syndrome 2010 pg 17