How Respiratory Disease is Informing Gastrointestinal Research
June 3, 2010
By Kate Johnson
For a gastroenterologist, Nicholas Talley takes an unusual interest in his patients’ respiratory symptoms. He also considers their dermatologic history a vital part of his work-up. As professor and chair of internal medicine at Jacksonville’s Mayo Clinic College of Medicine Dr. Talley is refreshingly willing to step outside of his field of specialty to gather clues and gain insight into the roots of gastrointestinal dysfunction.
In a recent issue of Nature Reviews Gastroenterology & Hepatology, he and his colleagues shared their observations about the common co-occurrence of certain gut and lung disorders, suggesting complaints from both ends might share the same cause and perhaps, in the future, might also share one treatment.
In fact, now that spring has sprung, if you suspect that asthma and allergies may also upsetting your stomach, Dr. Talley believes you may be right.
He, along with some other respiratory and gastrointestinal researchers suspect that the same things which make noses itch and asthmatic lungs flare may also be causing similar inflammation in the digestive tract.
In other words, allergic symptoms may run from one end of the gut to the other.
The good news is, while asthma and hayfever therapies have not yet been designed for the gut, researchers are looking into it. In the meantime there are other suggestions to minimize stomach complaints during allergy season.
The link that Dr. Talley sees between the gut and the lungs, may be due to an influx of cells called eosinophils.
In his recent paper (Nat. Rev. Gastroenterol. Hepatol. 7, 146–156 (2010), he and his colleagues describe how patients with asthma and allergic rhinitis have abnormally high levels of eosinophils in both their airways and their intestines.
Eosinophils are important immune system cells that are made in the bone marrow and normally line the mucous membrane in the stomach, small intestine and colon.
In health, these cells are not normally found in the airway at all – their main purpose is defend against bugs and toxins and prevent them from being absorbed into the body.
But in some people with asthma and allergies, the eosinophilic response is exaggerated, and exposure to allergens can trigger an excess of these cells – in both the gut and the lungs.
As a result, in addition to wheezing and sneezing, patients may also be bloated and gassy.
“I don’t think respiratory researchers have been terribly excited about gut problems, but I bet a lot of their asthma patients have gut problems if they ask them,” said Dr. Talley in an interview.
“I most certainly have seen patients with severe forms of asthma that have a pretty profound gastrointestinal (GI) component,” said Dr. Sally E. Wenzel Professor of Medicine, and Director of the University of Pittsburgh Asthma Institute. “A history of diarrhea and GI distress is not that uncommon [in asthma] and it’s not inconceivable that there is a relationship with eosinophils,” she said, adding that among the different types of asthma, some are considered to be linked to eosinophils while others are not.
This distinction in asthma – between eosinophilic versus non-eosinophilic disease – suggests exciting diagnostic and treatment possibilities for the field of gastroenterology, which is hampered by vague symptoms and imprecise therapies.
“Just as there are different types of asthma, there are probably different types of gut diseases that may or may not be related to eosiniphils – even though they may look similar clinically,” said Dr. Talley.
“Perhaps if we have modes of identifying people with eosinophil-related problems, for example by histological tissue examination, we might have a better chance at making precise diagnoses and prescribing targeted treatment,” he said. “It’s a totally different way of thinking about this, which is why we’re excited about it.”
Early support for this notion can be seen in asthma patients who quite commonly suffer from gastroesophageal reflux disease (GERD), or a more severe condition known as eosinophilic esophagitis (EE). While the precise cause of these overlapping lung-gut conditions is still being debated – eosinophilic excess is present in both, though much more profoundly in the latter.
“We thought wow, hang on, we can distinguish these things not by symptoms but by looking at what’s going on with their eosinophils,” he said. Perhaps the same could be done in irritable bowel syndrome, which is also linked to asthma.
“By looking for these subtle inflammatory changes (through biopsy) and by profiling and categorizing people based on these results, we think then you might be able to say this person has a particular profile, and we would treat them in one way, whereas this other person who has similar symptoms does not have that profile and we will have to find a different treatment approach,” he said. “We strongly suspect that this is the approach that will lead to significant benefits for subsets of patients in the future – rather than treating everyone with the same symptom profile in the same way and hoping they get better. In other words, we’d like to target treatment at pathology, rather than symptoms.”
Although eosinophils are normally protective in the gut, in allergy, a glut in the lungs and gastrointestinal tract reverses their function, causing damage to the mucous membranes. When this happens, the protective barrier in the gut is broken, allowing toxins to leak into the circulation. This increased intestinal permeability, or “leaky gut” has been documented in asthma sufferers.
“If you’re experiencing feelings of fullness, bloating, can’t finish your meal, or have pain in your stomach – it’s more likely to be associated with eosinophils,” said Dr. Talley. “With lower gut symptoms – constipation, diarrhea, and lower abdominal pain – we found these people don’t have excess eosinophils.”
Although inhaled asthma and nasal allergy treatments can alleviate respiratory symptoms, they have little chance of relieving gut complaints. Systemic asthma treatments aimed specifically at reducing eosinophils could offer gastrointestinal promise, but this approach still needs to be explored.
And while respiratory symptoms may wax and wane with the seasons, gastrointestinal symptoms may wind up becoming chronic, requiring a more permanent solution.
“You can continue to have the gut inflammation and to be symptomatic longterm even though perhaps the allergens are not always there,” says Dr. Talley.
So, what can be done right now for the allergically-challenged gut?
“Clearly diet is going to be the big key here,” says Dr. Talley.
If part of the problem is intestinal permeability, what about repairing the protective barrier and avoiding foods that irritate the fragile gut?
Food is rarely the cause of asthma or other respiratory symptoms, says Dr. Wenzel – so the initial trigger for eosinophil overgrowth is most likely inhaled allergens. But once the gut is inflamed, and intestinal permeability becomes compromised, certain foods might present a daily dose of irritation. Sometimes foods that are managed fine in a healthy gut can stir up trouble, or even allergy in an inflamed one.
In fact, avoidance of the six most common food allergens (cow’s milk protein (casein), soy, wheat, egg, peanut/tree nuts, and seafood) has been shown to significantly improve symptoms in patients with eosinophilic esophagitis.
What about repairing the leaky gut, so that toxins can’t pass through the intestinal lining?
A recent study in celiac disease, an intestinal disorder marked by intestinal permeability, showed that probiotic treatment with bifidobacteria had an anti-inflammatory effect (J Leuk Biol. 2010 87: 765) on intestinal cells. And there is promising data for the same probiotic in irritable bowel disease, though no data looking at upper gut syndromes, says Dr. Talley.
Finally, there is some evidence that a low-fat diet may calm inflammatory processes. A brand new study comparing high and low-fat diets showed the latter significantly reduced airway inflammation and improved response to asthma medications.
Perhaps this diet might have similar anti-inflammatory effects in the gut.
At the very least, it’s another hint that what’s happening at the intestinal interface may have may have far-reaching percussions throughout the body.