Charles E. King

Small Intestine Bacterial Overgrowth

The gastrointestinal tract proximal to the distal ileum is usually sparsely populated with bacteria. When overgrowth of bacteria in the small intestine is accompanied by nutrient malabsorption and clinical manifestations of weight loss and malnutrition, the setting has been called the stasis, stagnant loop, or blind loop syndrome. Since the publication of a number of excellent general reviews of the subject several years ago, 1–4 there has been an increased understanding of some of the pathophysiologic events accompanying overgrowth of bacteria in the small intestine. In particular attention has been drawn to the potential addition of mucosal injury to disturbances of the intraluminal environment in the altered handling of various nutrients. In addition, clinical recognition of the entity has increased with the use of noninvasive screening tests, with improvement in culture technique, and with increased recognition of several types of disordered intestinal motility predisposing to overgrowth. The purpose of this review will be to (a) analyze recent developments in the understanding of this syndrome, putting them into perspective with the previously reviewed material; (b) point out the clinical ramifications of the recent information, especially with the perspective that most conditions predisposing to bacterial overgrowth are lifelong, once present; and (c) suggest several areas where future investigation might prove fruitful in furthering our understanding of the pathophysiology and management of small intestine bacterial overgrowth.

Comparison of the 1-gram [14C]xylose, 10-gram lactulose-H2, and 80-gram glucose-H2 breath tests in patients with small intestine bacterial overgrowth.

The sensitivity of three breath tests (1-g [14C]xylose, 10-g lactulose-H2, and 80-g glucose-H2) was studied in 20 subjects with culture-documented small intestine bacterial overgrowth. Elevated breath 14CO2 levels were seen within 30 min of [14C]xylose administration in 19 of 20 subjects with bacterial overgrowth and 0 of 10 controls. In contrast, H2 breath tests demonstrated uninterpretable tests (absence of H2-generating bacteria) in 2 of 20 subjects with bacterial overgrowth and 1 of 10 controls and nondiagnostic increases in H2 production in 3 of 18 glucose-H2 and 7 of 18 lactulose-H2 breath tests in subjects with bacterial overgrowth. These findings demonstrate continued excellent reliability of the 1-g [14C]xylose breath test as a diagnostic test for bacterial overgrowth, indicate inadequate sensitivity of H2 breath tests in detecting bacterial overgrowth, and suggest the need for evaluation of a 13CO2 breath test having the same characteristics as the [14C]xylose test (avidly absorbed substrate having minimal contact with the colonic flora) for nonradioactive breath detection of bacterial overgrowth in children and reproductive-age women.

Clinically significant vitamin B12 deficiency secondary to malabsorption of protein-bound vitamin B12

Protein- (chicken serum) bound [57Co]cyanocobalamin absorption was evaluated in five hypochlorhydric patients who had developed B12 deficiency despite having normal absorption of unbound crystalline vitamin B12. All five patients had decreased urinary excretion of protein-bound B12 (0.06–0.34%) as compared to twelve normal controls (0.61–5.6%), P<.001. Improvement in protein-bound B12 absorption in four of the five patients occurred with the exogenous administration of hydrochloric acid, pepsin, gastric intrinsic factor, or a combination thereof. Vitamin B12 deficiency developing in the setting of hypochlorhydria may result from deficiency of acid-peptic digestion of B12 bound to protein and/or a relative deficiency of intrinsic factor. This digestive defect is not detected with tests which measure the absorption of unbound crystalline B12 but is detected by a simple test which employs B12 bound to chicken serum as the form of protein-bound B12.

Malabsorption of protein-bound cobalamin but not unbound cobalamin during cimetidine administration

The suppressive effects of cimetidine on acid, pepsin, and intrinsic factor secretion have been well documented; however, the effect of cimetidine on cobalamin absorption has not been assessed. The absorption of both unbound [57Co] cyanocobalamin and protein-bound [57Co] cyanocobalamin was evaluated in 12 patients with duodenal ulcer disease during and after discontinuation of cimetidine therapy. Cimetidine administration did not lead to malabsorption of unbounds cobalamin but caused malabsorption of protein-bound cobalamin (0.22±0.08%, [mean±1sem] versus 2.3±0.10% in control subjects,P<0.01). This malabsorption was reversible upon discontinuation of cimetidine. Patients on cimetidine therapy malabsorb protein-bound cobalamin and, during long-term treatment, are at risk for developing cobalamin deficiency. This malabsorption of protein-bound cobalamin is not detectable by the usual tests of cobalamin absorption which employ unbound cobalamin.