Heartburn, also called gastroesophageal reflux disease (GERD), is the most common digestive disorder in the US, and the acid-suppressing drugs used to treat it can have dangerous side effects after long-term use.
The prevailing belief by the public, and even many conventional doctors, is that reflux is caused by having too much stomach acid, hence the standard treatment with antacids and PPIs. But we now know that GERD is not a disease of excess stomach acid, and many GERD patients actually produce lower levels of stomach acid than normal.
In light of this evidence, it seems logical that heartburn must be caused by stomach acid inappropriately entering the esophagus. And indeed, tests for esophageal acid contact time have confirmed that most patients with GERD do have above-normal acid contact time over a 24 hour period. (1)
As I’ve discussed in the past, one cause of increased acid reflux into the esophagus is dysfunction of the lower esophageal sphincter (LES), a valve that separates the esophagus from the stomach. This dysfunction can be caused by increased intra-abdominal pressure, which often results from bacterial overgrowth in the small intestine. This has been one of the prevailing theories about the underlying cause of reflux for several years now, but it has some limitations.
Not all GERD patients have abnormal amounts of acid reaching their esophagus
As I just mentioned, most GERD patients do have above-normal acid contact time. But most is not all. In fact, 24-hour acid contact tests have found that up to 30% of GERD patients actually have normal acid contact time. (2, 3)
Some patients with GERD symptoms even have normal endoscopy results - their esophagus looks the same as a healthy person’s esophagus. These patients are considered to have ‘non-erosive reflux disease,’ or NERD, and up to half of NERD patients have normal acid contact time. (4)
So, what separates a healthy individual from a GERD or NERD patient with normal acid contact time? If there isn’t too much stomach acid reaching the esophagus, what is causing the heartburn?
One theory gaining traction in the scientific community to describe this phenomenon is the idea of impaired epithelial barrier function. In other words - GERD might be a result of “leaky esophagus.”
Is a “leaky esophagus” the cause of your acid reflux? #gerd #heartburn
What is “leaky esophagus”?
You’ve probably heard of “leaky gut” before. Cells in the epithelial lining of the intestine are held together by tight junctions, and if these tight junctions are disrupted, particles that wouldn’t normally be absorbed make their way through the lining of the intestine and into the bloodstream. This can cause a host of problems, from food allergies to autoimmunity and more.
“Leaky esophagus” is a similar concept. It’s actually normal for acid and stomach contents to reflux into the esophagus occasionally. (5) In a healthy esophagus, this acid can’t penetrate the cell membrane of the epithelial cells, and tight junctions prevent it from getting in between the cells.
In fact, normal esophageal tissue is remarkably resistant to acid. In acid perfusion (or “Bernstein”) tests, acid is dripped directly onto the esophagus through a tube that is inserted through the nose (sounds pleasant, right?), and healthy people don’t experience any pain or heartburn, even after half an hour. (6)
However, if those tight junctions are disrupted, acid can make its way between the epithelial cells, decreasing the pH of the intracellular space. Since even small pH changes in this area are threatening to the body, there are pain receptors located close to the epithelial lining, and they send pain signals to the brain in response to the lower pH. These signals are interpreted by the brain as heartburn. Unsurprisingly, patients with NERD or GERD who receive the Bernstein test experience discomfort almost immediately.
As further evidence of the presence of leaky esophagus, biopsies of GERD and NERD patients almost always reveal dilated intracellular spaces, which is a marker for impaired barrier function. (7) These dilated spaces are increasingly being accepted as a hallmark symptom of both NERD and GERD.
Is leaky esophagus a cause or a symptom of reflux?
It appears that leaky esophagus is present in most cases of GERD. But it’s not clear whether leaky esophagus is a cause of reflux, or just another side effect.
Even though a healthy esophagus is resistant to acid, high levels of acid exposure over time will eventually lead to inflammation and impaired barrier function. In this case, increased acid exposure comes first - most likely due to a dysfunctional LES - and leaky esophagus is not the root cause; it’s just another symptom.
However, there maybe some reverse causality, particularly in GERD patients who have normal acid contact time. In this case, something other than acid exposure disrupts the epithelial tight junctions, which causes heartburn even at normal acid levels. Over time, this “leaky esophagus” can lead to the visible epithelial tissue damage observed in GERD patients.
This happens because the “back” side of an epithelial cell is not as resistant to acid as the “front” is, so once the acid seeps through the tight junctions, it can enter cells from the back and cause cell death and tissue damage. (8)
Unfortunately, this process can actually lead to LES malfunction and increased acid exposure, creating a vicious cycle. Now, increased acid exposure in the esophagus is a symptom of GERD, rather than the root cause.
What causes leaky esophagus?
So if leaky esophagus happens first in some cases of GERD, what causes leaky esophagus in the first place?
One possibility lies in the esophageal microbiome. The esophagus houses a community of microbiota similar in complexity to the intestinal microbiome, and the makeup of this bacterial community is different in healthy people compared to people with GERD. The microbes found in the esophagus of GERD patients are primarily gram-negative, while the microbes in the esophagus of healthy people are primarily gram-positive. (9)
Increased numbers of gram-negative bacteria can trigger inflammation by exposing epithelial cells to lipopolysaccharides (LPS), a component of gram-negative bacteria that causes immune responses in the body. (10) The inflammatory cytokines released in response to LPS can then lead to loss of tight-junction integrity, resulting in esophageal permeability. (11, 12)
Exposure to LPS can also cause the LES to relax, promoting reflux and increasing acid exposure time - again, creating a vicious cycle. (13)
Unfortunately, there isn’t a lot of research yet that clarifies the causes of increased esophageal permeability. But if the mechanisms at work in the esophagus are similar to those in the intestines, other probable causes could be stress, excessive alcohol consumption, and excessive use of non-steroidal anti-inflammatory drugs (NSAIDS). (14, 15, 16, 17)
All of these factors can contribute to leaky gut, so it wouldn’t be surprising if they contributed to leaky esophagus as well.
What does this mean for heartburn sufferers?
As you can see, GERD is a complex and multifaceted disorder with no single cause or presentation. Luckily, all of the strategies for healing heartburn and GERD that I’ve been recommending for years would also be expected to heal leaky esophagus.
A low-carb Paleo diet, gut-healing foods like bone broth and fermented foods, regular stress-management, and a focus on balancing the intestinal (and esophageal) microbiome with probiotics and prebiotic foods are always good approaches to treating the root cause of GERD.
Now I’d like to hear from you. Have you cured your heartburn using a Paleo diet? What other strategies have worked for you? Share your story below!