Glycocholate Breath Test

14C-glycocholate breath test or bile acid test is based on the bile salt deconjugating capacity of bacteria in the proximal small bowel. Conjugated bile acids are excreted through the bile in the duodenum, and they are reabsorbed in the terminal ileum. Conjugated bile acids are in the enterohepatic circulation. Physiologically, less than 5% of the conjugated bile acids reach the colon. After excretion in the duodenum, bile acids stimulate micellization of dietary lipids. After oral administration of glycocholic bile acid (a normal component of bile) this is normally reabsorbed in the terminal ileum. In cases of SBBO some bacteria split off glycine on the amide bond of cholylglycine. Glycine is absorbed, and fermented in the liver to CO2, H2O, and ammonia (NH4); the CO2 produced is exhaled. When using 14C glycocholate, the 14CO2 in the exhaled air can be measured.

The sensitivity is too low (20-70%) to allow SBBO to be demonstrated without additional intestinal culturing. A rise in labeled CO2 does not differentiate bile salt wastage from bacterial overgrowth. This is a disadvantage given that a significant number of SBBO patients may have had ileal resection. Ruling out bile salt malabsorption as an explanation for a positive breath test can be done with stool collection (42,77).

The false negative rate for the 14C-glycocholate breath test is 30-40%. There are three reasons for false negative outcomes. Firstly, one needs anaerobic organisms to deconjugate bile salts. Secondly, not all cases of bacterial overgrowth involve bile salt deconjugation. Lastly, the fatty meal (usually a polymeric supplement) given with the cholylglycine may, in theory, affect the ratio of labeled and unlabeled carbon dioxide absorbed, diluting the labeled carbon dioxide with that produced from the metabolism of the meal. False positive results are possible in case of ileal pathology, ileal resection, and increased intestinal transit. In those cases bile acids are deconjugated by the (anaerobic) colonic microbiota. The disadvantage of using radioactivity in 14C-substrate breath tests can be overcome by using the stable 13C-isotope, which is measured by mass spectrometry in breath samples. However, the use of 13C -isotope does not improve the sensitivity.

14C-D-xylose Breath Test

The 14C-D-xylose breath test was considered to be the only breath test for the detection of bacterial overgrowth with high sensitivity (95-100%) and 100% specificity, but these promising results have not been sustained (42). Compared with cultures of the duodenal aspirates, the sensitivity and specificity are 60% and 40%, respectively (78).

This test is based on the assumption that the overgrown aerobic Gram-negative microbiota ferment D-xylose. The 14CO2 produced, and unmetabolized xylose are absorbed by the proximal small bowel, which thus avoids confusion of results caused by metabolism of substrate by colonic bacteria. Subjects must fast at least 8 hours before the test, and no smoking or exercise is permitted for 12 hours before the breath test. Following a 1 g oral dose of 14C-D-xylose in water, elevated 14CO2 levels are detected in the breath within 60 minutes in 85% of patients with SBBO.

False negative rates for the 14C-D-xylose breath test are 35-78%. False negative results cannot be entirely attributed to the absence of D-xylose fermentation of the microbiota (overgrown bacteria in 81.8% of SBBO patients are capable of D-xylose fermentation); body weight is correlated to endogenous CO2 production, and should therefore also be taken into account (79). Disturbed gastric emptying and small intestinal motility can also contribute to a false-negative result of the 14C-D-xylose breath test because of delayed delivery of the labeled substrate to the metabolizing microbiota. Refinement of the 14C-D-xylose breath test to include a transit marker for intestinal motility increases its specificity. With the transit marker one can determine whether the site of metabolism is in the small intestine or the colon (80).

Lactulose Hydrogen Breath Test

Lactulose is an easily fermented disaccharide, and is used for the detection of bacterial overgrowth, and for determination of the orocecal transit time. The lactulose hydrogen breath test is a simple, inexpensive, and noninvasive technique to diagnose SBBO. The lactulose breath test is performed after 12 hours fasting previous to the test. Hydrogen breath samples are taken at baseline, and subsequently every 10-30 minutes after the test meal that contains 10-12 g of lactulose. The hydrogen breath samples are analyzed gas chromatographically (81). Baseline samples average 7.1 +5 parts per million (ppm) of H2 and 0-7 ppm for CH4 (82). Values of the baseline sample over 20 ppm H2 are suspect for bacterial overgrowth. Values between 10 and 20 suggest incomplete fasting before the test or ingestion of slowly digested foods the day before the test, the colon being the source of the elevated levels (82). Slowly digested foods like beans, bread, pasta, and fiber must not be consumed the night before the test because these foods produce prolonged hydrogen excretion (82). The patient is not allowed to eat during the complete test. Antibiotics and laxatives must be avoided for weeks prior to breath hydrogen testing. Cigarette smoking, sleeping, and exercise must be avoided at least a half hour before and during the test because these may induce hyperventilation (42). Chlorhexidine mouthwash must be used before the test to eliminate oral bacteria, which might otherwise contribute to an early hydrogen peak after the substrate is given. Lactulose, which reaches the colon, shows peaks usually more than 20 ppm above baseline after 2-3 hours of testing. Lactulose is not absorbed in the small intestine so every patient should have a colonic peak, assuming the colonic microbiota has not been altered. Peaks associated with SBBO occur within 1 hour, and are less prominent. Some laboratories measure H2 and CH simultaneously whereas others test CH4 selectively after flat lactulose tests (42). Figure 3 shows lactulose breath test results in a patient with small bowel bacterial overgrowth.

The lactulose hydrogen breath test is positive for small intestinal bacterial overgrowth if there is an increase in breath hydrogen of > 10 parts per million above basal that occurs at least 15 minutes before the cecal peak. Strict interpretative criteria, such as requiring two consecutive breath hydrogen values more than 10 ppm above the baseline reading, and recording a clear distinction of the small bowel peak from the subsequent colonic peak (double peak criterion), are recommended. Application of the double peak criterion alone for interpretation of the lactulose hydrogen breath test is inadequately sensitive, even with scintigraphy, to diagnose bacterial overgrowth. Twenty-seven percent of normal subjects have no peak due to organic acid reduction or dilution from voluminous diarrhea (42).

The disadvantage of this test is that it is not always easy to distinguish breath hydrogen arising from small bowel colonization from that resulting from cecal fermentation in patients with an exceptionally rapid orocecal transit time. A comparison with the jejunal culture sensitivity of 68% and specificity of 44% has been described (51). A sensitivity of 16% for SBBO has been described (83).

Despite the attractive aspects of ease of performance and avoidance of a radioactive tracer, breath hydrogen tests are not sufficiently sensitive or specific to justify their substitution for the 14C-D-xylose breath test for noninvasive detection of intestinal bacterial overgrowth.

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  • regina
    How is co2 produced from dxylose?
    8 years ago

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