2. BACTERIAL OVERGROWTH
ο The proximal small intestine (duodenum and
jejunum) normally contains few bacteria.
ο Most ingested bacteria do not survive the acidic
environment of the stomach and therefore few
live organisms normally enter the small bowel.
ο The motility of the jejunum prevents fecal-type
organisms from progressing up into the jejunum
from the cecum.
ο The ileum normally contains some fecal-type
bacteria.
3. BACTERIAL OVERGROWTH
ο Colonization of the upper small bowel is
described as bacterial overgrowth
ο and usually occurs as a consequence of
other abnormalities (structural or motility
disorders) of the small intestine
4. PATHOGENESIS
ο Defense against SIBO
β Gastric acid
β Intestinal motility
β Intact ileo-cecal valve
β Immunoglobulin's
β Bacteriostatic properties of pancreatic and
biliary secretion
6. COMPLICATIONS
ο The bacteria colonizing the small bowel
(such as Escherichia coli) deconjugate and
dehydroxylate bile salts, leading to
conjugated bile salt deficiency, which causes
fat malabsorption.
ο Bacterial metabolism of vitamin B, may also
occur, leading to vitamin B deficiency
8. DIAGNOSIS
Gold standard method
ο Small-bowel aspiration for quantitative
culture traditionally has been regarded as the
gold standard for the diagnosis of SIBO.
ο Because it is imperative not to contaminate
the sample.
ο aspiration is performed either through an
endoscopically or fluoroscopically.
9. ο Limitations
ο Cost.
ο Invasive nature.
ο Time commitment,
ο Lack of adequate validation.
ο Accuracy of culturing.
ο the potential for missing distal small-bowel
bacterial overgrowth.
10. BREATH TESTING
ο readily available.
ο Safe.
ο inexpensive.
ο noninvasive
ο alternative to jejunal aspiration culture for the
diagnosis of SIBO.
11. PRINCIPLE OF BREATH TEST
ο By measuring exhaled gases produced by
bacterial fermentation of various orally
ingested substrates, the bacterial load within
the small bowel can be assessed indirectly.
ο The measured gases can include labeled
carbon dioxide (CO2), hydrogen, and
methane.
12. ο For the labeled CO2 studies, the orally ingested
substrates include
ο 14C-glycocholate
ο 13C-glycocholate
ο 14C-xylose,
ο 13C-xylose
ο hydrogen and methane breath testing, the
substrates include
ο glucose
ο lactulose
13. CARBON DIOXIDE BREATH TESTING
ο Testing used either the radioactive isotope of carbon,
14C or the nonradioactive 13C isotope.
ο Limitations
ο One of the greatest challenges with CO2 breath
testing was correcting for the endogenous CO2
production
ο which differed considerably in the various disease
states adversely affecting test accuracy.
ο Furthermore, the process of conjugating substrates
with labeled carbon added to the cost and limited
availability.
ο For these reasons, CO2 breath testing has been
abandoned in clinical practice.
14. 14C-GLYCOCHOLATE BREATH TEST
ο The principle underlying the use of
glycocholic acid was that
ο under normal circumstances, bile acids
readily were absorbed in the ileum.
ο Any unabsorbed glycocholic acid was subject
to metabolism, either by bacteria in the
proximal small bowel before ileal absorption,
or in the colon in the event of glycocholate
malabsorption.
15. ο When there is bacterial overgrowth,the
bacteria deconjugate the glycocholic acid to
produce 14C-glycine that is absorbed and
metabolized with an increase in breath
I4CO2.
ο A subsequent increase in labeled CO2 in
expired breath within 6 hours was interpreted
as a positive study.
16. LIMITATIONS
ο inability to distinguish small bowel from
colonic bacterial deconjugation of the
glycocholic acid
ο decreased accuracy with underlying rapid
small-bowel transit.
ο A compounding concern is the theoretical
risk of long-term radiation exposure with the
14C-labeled substrates
17. 13C/14C D-XYLOSE
ο D-xylose is a poorly absorbed 5-carbon
monosaccharide found in plants.
ο D-xylose labeled with either 13C or 14C was
ingested orally, and metabolized by gut bacteria
yielding labeled CO2 measured in the breath.
ο However, D-xylose is variably absorbed and
metabolized,
ο which can blur the baseline breath CO2
measurements,
ο making it more difficult to measure labeled CO2
production in the setting of SIBO.
18. ο Limitations
ο D-xylose may be a poor metabolic substrate for
common coliform bacteria including Escherichia
coli, enterococci, and clostridia.
ο thereby increasing the risk of false-negative
results.
19. HYDROGEN AND METHANE BREATH TESTING
ο Patient Preparation
ο Avoidance of wheat-based foods and fiber for
12 hours before.
ο Fasting breath hydrogen is typically <5 ppm (5
pL1L) and concentrations 20 ppm (20 pL/L) may
be an indication of malabsorption or bacterial
overgrowth.'"
ο Oral hygiene before ingestion of the substrate in
hydrogen breath tests minimizes the production
of hydrogen by oral bacteria.
20. ο Brushing of teeth or use of an antibacterial
mouthwash (e.g., 1% chlorhexidine) is
recommended.'"
ο Mouthwash containing alcohol should not be
used, because this may interfere in the
measurement of hydrogen.
ο Cigarette smolie contains high hydrogen
levels and smoking is therefore not permitted
immediately before or during the test.
21. ο Hydrogen breath testing was introduced as an
alternative to CO2 breath testing for SIBO.
ο Hydrogen breath testing is based on the
principle that bacterial metabolism
(fermentation) of nonabsorbed carbohydrates is
the sole source of hydrogen and methane in
exhaled breath.
ο ource of hydrogen and methane in exhaled
breath. After the oral ingestion of various
substrates, hydrogen can be measured in
exhaled breath using gas chromatography and
reported as a concentration in parts per million
(ppm).
22. ο Methane can be measured in a similar
manner to hydrogen.
23. LACTULOSE BREATH TEST
ο Lactulose (usually given in a dose of 10 g in
200 mL water) is a nonabsorbahle
disaccharide.
ο In a normal subject, breath hydrogen does
not increase until the lactulose enters the
large intestine; the time from ingestion to a
rise in breath hydrogen is therefore normally
an indication of small bowel transit time.
24. ο In bacterial overgrowth, there is an early rise
in breath hydrogen of at least 20 ppm within
30 minutes of ingestion of lactulose.
ο The early increase is diagnostic when it can
be distinguished clearly from the later colonic
rise. Frequent measurements (e.g., at 5-
minute intervals) are essential in the first 30
minutes, with measurements every 15
minutes thereafter for up to 3 hours.
25. GLUCOSE BREATH TEST
ο Glucose is a monosaccharide that is completely
absorbed in the proximal small intestine under
normal physiologic conditions.
ο However, in the presence of SIBO, glucose is
fermented by bacteria before it can be absorbed
in the proximal intestine.
ο an individual with SIBO, the proximally
displaced bacteria theoretically should lead to
the fermentation of glucose and a resultant
increase in breath hydrogen excretion.
26. ο 50 g glucose dose in 250 mL of water, with
breath samples collected every 15 minutes
for a total of 120 minutes, and a positive test
defined as an increase in hydrogen levels by
12 ppm or more from baseline.
ο In bacterial overgrowth, breath hydrogen
usually increases within 75 minutes of
ingestion of glucose and sometimes within
30 minutes.
27. ο The finding of an increased fasting breath
hydrogen has high specificity for bacterial
overgrowth but poor sensitivity.
ο however, a fasting breath hydrogen >15 ppm
and an increment of at least 12 ppm within 2
hours of a 50 g glucose challenge is
diagnostic of bacterial over growth.
28. ο Limitation
ο Variations in gastric emptying rate and
small bowel transit times are problems that
livnit the diagnostic accuracy of the breath
hydrogen tests.
29.
30. Reference
ο Teatz text book of clinical bio chemistry (4 th
edition )
ο Richard J. Saad and William D. Chey. Breath
Testing for Small Intestinal Bacterial
Overgrowth: Maximizing Test Accuracy
2014;12. (https://sibotesting.com/wp-
content/uploads/2015/10/SIBO-Testing-
Article.pdf )