Hydrogen Breath Tests for Diagnosis of Carbohydrate Malabsorption and Small Intestinal Bacterial Overgrowth

Allen A. Lee, MD

Jason R. Baker, PhD

Hydrogen breath tests (HBTs) are common, noninvasive, but indirect tests to aid in the diagnosis of common gastrointestinal conditions, such as carbohydrate malabsorption and small intestinal bacterial overgrowth (SIBO).
The principal gases produced in the gastrointestinal tract include hydrogen (H₂), carbon dioxide (CO₂), and methane (CH₄) with lesser contributions from nitrogen (N₂) and oxygen (O₂).¹
HBTs are based on the principle that H₂ and CH₄ are produced exclusively by bacterial fermentation in the human gut.²
An orally administered carbohydrate will be rapidly metabolized in the small intestine in the setting of SIBO or in the colon with carbohydrate malabsorption leading to production of H₂ and/or CH₄.
These gases can then traverse the intestinal mucosa where it is absorbed into the systemic circulation, excreted into the lungs and can be measured in expired breath (Fig. 56.1).
One of the main drawbacks of the HBT is the lack of a validated gold standard for diagnosing carbohydrate malabsorption and SIBO.
In addition, there is lack of standardization regarding methodology of test across different studies and centers.
This has produced considerable heterogeneity in terms of the indications, techniques, and interpretation of test results.
Recently, European and North American consensus guidelines have been published in an attempt to standardize HBT.³,⁴
This chapter will focus on the indications, methodology, interpretation, and limitations of HBT for the diagnoses of lactose malabsorption and SIBO.

FIG. 56.1 A schematic diagram that shows principle of hydrogen breath test. ppm, parts per million; SIBO, small intestinal bacterial overgrowth. (Reproduced with permission from Ghoshal UC. How to interpret hydrogen breath tests. J Neurogastroenterol Motil. 2011;17(3):312-317.)

CARBOHYDRATE MALABSORPTION

Lactose is a disaccharide found in milk and dairy products.
In the absence of sufficient lactase, malabsorbed lactose passes into the colon where it leads to an increased osmotic load.
Lactose is also readily fermented by colonic microbiota which results in production of H₂ and CH₄.
Lactose malabsorption may manifest with gastrointestinal symptoms, such as abdominal pain, bloating, diarrhea, and flatulence.
Lactase malabsorption may also occur secondary to other pathologic conditions in the small intestine, such as celiac disease, infectious gastroenteritis, or Crohn disease, which can lead to a decrease in lactase activity.
Presence of SIBO may also cause false-positive results of lactose and fructose BT.⁵ As such, tests to rule out SIBO are recommended prior to testing for carbohydrate malabsorption.
Other carbohydrates, such as fructose, can also be tested for malabsorption. Fructose is a naturally occurring sugar and is widely used as high-fructose corn syrup in many foods and
beverages. Fructose is incompletely absorbed even in healthy volunteers while fructose malabsorption has been proposed as a potential cause of unexplained GI symptoms.⁶,⁷
Sucrose, a disaccharide composed of fructose and glucose, is another important source of this carbohydrate.

SMALL INTESTINAL BACTERIAL OVERGROWTH

SIBO is a condition of overgrowth of aerobic and/or anaerobic bacteria in the normally relatively sterile environment of the small intestine.⁸
However, it remains a controversial topic as there is no universal agreement on the definition for SIBO.
Symptoms are nonspecific and may include abdominal pain, bloating, diarrhea, malabsorption, and weight loss.
Traditionally, SIBO was diagnosed by >10⁵ cfu/mL on quantitative culture from small bowel aspirate.
However, due to the invasiveness of the approach, high cost, difficulty avoiding oral contamination, and inability to sample further downstream in the small intestine, small intestinal culture has largely been replaced by noninvasive tests, such as HBT.

TEST PREPARATION

Based on North American Consensus guidelines,⁴ patients should prepare for breath testing (BT) in the following ways:
- Antibiotics should be avoided for at least 4 weeks prior to BT.
- A firm position statement cannot be reached due to lack of conclusive data on stopping or continuing pro/prebiotics prior to BT.
- Promotility drugs and laxatives should be stopped for at least 1 week prior to BT.
- Fermentable foods, such as complex carbohydrates, should be avoided on the day prior to BT.
- Patients should fast for at least 8 to 12 hours prior to BT.
- Patients should avoid smoking on the day of BT.
- Physical activity should be limited during the BT.
- Proton-pump inhibitors may be continued during BT.
Our center also recommends that patients avoid bismuth-containing products (e.g., Pepto-Bismol) for at least 2 weeks prior to testing as bismuth has antibacterial properties.⁹
We further recommend that patients eat a diet low in fiber, poorly absorbed carbohydrates and dairy for 2 days prior to BT as these can affect baseline H₂ levels.¹⁰,¹¹
Finally, poor oral hygiene can result in false-positive results. As a result, we administer an oral antibacterial mouthwash before ingestion of the carbohydrate substrate to minimize this risk.