Two new studies support the value of performing breath testing to aid selection of appropriate treatments for patients with common functional gastrointestinal symptoms. Data show these tests can help differentiate between IBS subtypes and distinguish IBS from sucrose malabsorption.
Investigators at Cedars-Sinai Medical Center, in Los Angeles, found that using breath tests to identify gut gas profiles can lead to more personalized and effective therapies for people with irritable bowel syndrome (Am J Gastroenterol 2022 Sep 6. doi:10.14309/ajg.0000000000001997).
By comparing data from two randomized controlled clinical trials, the researchers were able to link specific gas-producing microbial patterns in the intestinal tract to the IBS diarrhea- and IBS constipation-predominant subtypes.
“This is the first study ever that compares the phenotype of IBS—to the microbiome—to breath testing all at the same time, in a very carefully curated group of patients,” said Mark Pimentel, MD, the executive director of the Medically Associated Science and Technology Program at Cedars-Sinai and senior investigator on the study.
Three Gases Associated With Microbiome Subtypes
Dr. Pimentel and his co-investigators found two main micro-types of the microbiome on the diarrhea side—one is hydrogen-predominant and the other is hydrogen sulfide–predominant. The hydrogen sulfide micro-type predicts more severe diarrhea.
“On the constipation side, it’s all about methane and methanogens, and for the first time, we were able to identify the hydrogen-producing organisms that feed the hydrogen to the methanogens to make the methane,” Dr. Pimentel told Gastroenterology & Endoscopy News.
“The findings are different from what we expected. All three—hydrogen, hydrogen sulfide and methane—need to be measured with breath testing.”
Measurement of all these gases is important because hydrogen predicts bloating and mild diarrhea, hydrogen sulfide predicts more severe diarrhea, and methane predicts constipation (Table). “Getting rid of those gases, or the bugs that produce them, can have very meaningful benefits to the patients with these symptoms,” he added.
| Table. Gases Measured in Breath Testing And Associated Symptoms | |
| Gas measured | Predicted GI symptoms |
|---|---|
| Hydrogen | Bloating and mild diarrhea |
| Hydrogen sulfide | More severe diarrhea |
| Methane | Constipation |
Dr. Pimentel explained how breath tests actually show that hydrogen sulfide–producing organisms in the gut are elevated when that gas is seen in the breath. “It’s the same for methane. We see the exact methanogenic bug that’s producing the methane,” he noted. “And for hydrogen, we see the bugs that produce hydrogen. So, it’s a three-way validation. The gases that are measured are accurate to the microbiome.”
According to Brian Lacy, MD, PhD, a professor of medicine at Mayo Clinic in Jacksonville, Fla., who commented on the study, this research is important to the field for two main reasons. First, most studies measured only hydrogen and methane, excluding hydrogen sulfide. “Many in the field thought that something was missing because we recognized a discrepancy in data from studies. Some patients had very low hydrogen levels but not overly high methane, so was another gas being generated?” he said. “Now, we know that a third gas—hydrogen sulfide—may be playing a critical role in symptom development in some IBS patients.”
Dr. Lacy added that “more importantly, this study shows that we may be able to identify IBS subtypes based on the underlying predominance of certain bacteria in the gut microbiome.”
Dr. Pimentel said there has been an increased understanding over the past decade that IBS is partly a microbiome condition. “But being able to further define the microbiome, and to be able to use noninvasive tests like breath testing to represent the microbiome, will allow for new therapies to emerge for the treatment of both diarrhea and constipation subtypes of IBS,” he said. “This is a really important pivotal study heading toward new therapies for IBS on the basis of the microbiome.”
According to Dr. Lacy, “Dr. Pimentel should be credited not only with challenging how we think about the pathophysiology of IBS but also enlightening us on the gut microbiome and its importance in IBS.”
Breath Testing Distinguishes Sucrose Malabsorption From IBS
The value of breath tests was validated further by new research conducted at Weill Cornell Medicine, in New York City. Investigators found that patients with sucrose malabsorption often present with IBS symptoms, such as cramping, bloating, gas and diarrhea, and noninvasive breath tests may be useful in distinguishing between these conditions (Proc [Bayl Univ Med Cent] 2022 Aug 23. doi:org/10.1080/08998280.2022.2114070).
“The sucrose breath test is convenient because it’s performed at home and mailed in; it’s also noninvasive, which is advantageous during COVID,” said study author Christine L. Frissora, MD, from the Division of Gastroenterology and Hepatology at Weill Cornell Medicine.
The investigators conducted a chart review of 258 adults with chronic, unexplained GI symptoms who sought care at Cornell University Medical Center, in New York City, between Oct. 19, 2016 and Sept. 28, 2021. Patients whose symptoms were consistent with carbohydrate maldigestion were tested for sucrose malabsorption using a noninvasive hydrogen–methane or 13C-sucrose breath test.
The incidence of sucrose malabsorption from two different hydrogen–methane breath tests was 34.4% (Commonwealth Diagnostics) and 40% (Aerodiagnostics). Using the C-sucrose breath test, the incidence was 26.5%. Combined results indicated that 31% of the patients had sucrose intolerance.
In a subgroup of patients with positive breath tests, dietary counseling, education and/or enzyme replacement resulted in improvement of symptoms in 26 of 43 patients (60%) for whom follow-up data was available.
Dr. Frissora noted that lactose intolerance—and even fructose intolerance—are well-known disorders, but there is less awareness about sucrose intolerance, which can develop if the brush border of the small intestine is damaged by infection, nonsteroidal anti-inflammatory drugs, isotretinoin and/or inflammation. Less commonly, sucrase deficiency can be a congenital condition.
Sucrose intolerance, a form of carbohydrate malabsorption caused by sucrase–isomaltase deficiency, is more common than previously thought. Restricting sucrose ingestion will help decrease symptoms in sucrase-deficient patients in the same way that limiting lactose will help patients who are lactase-deficient. Minimizing the carbohydrates that are not well digested will improve the common symptoms of diarrhea, gas and bloating, Dr. Frissora pointed out. Patients also can choose to take the enzyme sacrosidase if they know they will be consuming sucrose.
“Sucrase deficiency causes IBS symptoms because the sucrose is not absorbed, and when it hits the colon, the bacteria have a ‘dinner party,’ the by-products of which cause the patient to feel they are ‘fermenting,’ which in fact they are,” Dr. Frissora said. “It is intuitive to me that malabsorption creates IBS symptoms, but sometimes everything is lumped into ‘IBS’ when certain disorders could be weeded out a bit better.”
Dr. Frissora and her co-investigators maintain that breath testing for sucrose intolerance should be considered for patients who present with unexplained symptoms of carbohydrate malabsorption, especially those who are not responding to traditional IBS therapies and diets. They plan to compare disaccharide biopsy results (the gold standard for diagnosing sucrase deficiency) with breath test results in these patients.
In an interview with Gastroenterology & Endoscopy News, Dr. Lacy commented on the study’s strengths. “It addresses an important issue. Sucrase deficiency in adult patients with persistent symptoms of gas and bloating has not been well studied. It may be more common than we think, and thus checking patients with persistent symptoms of gas and bloating who have failed other dietary interventions (avoiding lactose, avoiding fructose, avoiding excess fiber and FODMAPs [fermentable oligo-, di-, monosaccharides and polyols]) is reasonable,” he said. “We do know that the low-FODMAP diet does not specifically exclude sucrose, so checking for sucrase deficiency in patients who fail the low-FODMAP diet is not unreasonable.”
He added that sucrose breath testing of patients who had been checked for other causes of bloating and gas (and were negative for deficient lactase, fructose and/or small intestinal bacterial overgrowth) “might be clinically useful and may lead to therapeutic changes.”
—Meg Barbor, MPH
Dr. Frissora reported a financial relationship with QOL. Dr. Lacy reported financial relationships with Gemelli, Ironwood, Salix, Sanofi and Takeda. Dr. Pimentel reported financial relationships with 9meters, Bausch, Ferring, Gemelli, Salvo, Synthetic Biologics, Vibrant and Vivante.
This article is from the November 2022 print issue.