Small Bowel Bacterial Overgrowth is a Common Cause of Chronic Diarrhea

Marcus Teo; Stephen Chung; Lauri Chitti; Cuong Tran; Stamatiki Kritas; Ross Butler; Adrian Cummins

Disclosures

J Gastroenterol Hepatol. 2004;19(8) 

In This Article

Abstract and Introduction

Background and Aims: Often a cause for chronic non-specific diarrhea (≥3 stools per day for more than 4 weeks) is not identified. Small bowel bacterial overgrowth (SBO) can occur without morphological damage and remains difficult to diagnose. Often diarrhea is treated empirically with antibiotics with a good response. The aims of the present study were first to investigate the prevalence of SBO in a consecutive series of patients with chronic diarrhea and second to compare the utility of duodenal fluid culture and 14C-D-xylose breath/lactulose test in diagnosing SBO.
Methods: In the first study, the cause of chronic diarrhea was prospectively diagnosed in 87 subjects. In the second study, tests of SBO were compared in 18 subjects with chronic diarrhea and 15 subjects with reflux oesophagitis used as control subjects. Duodenal fluid was aspirated at endoscopy and cultured and later a 14C-D-xylose breath/lactulose test was performed.
Results: In the first study, SBO was present in 48% of those with chronic diarrhea. In the second study, the diarrhea group had an average (range) stool frequency of 5.5 (3-10) per day and had normal duodenal biopsies. A total of 33%, 50%, 67% of subjects had SBO by duodenal culture alone, by a 14C-D-xylose breath/lactulose test alone and by a combination of both tests, respectively. In the control group, 0%, 13% and 13% had SBO by duodenal culture alone, by 14C-D-xylose breath/lactulose test alone and by combination of tests, respectively.
Conclusion: Small bowel bacterial overgrowth is a common (33-67%) cause of chronic diarrhea.

In the Western world, the common causes of chronic diarrhea are irritable bowel syndrome, inflammatory bowel disease, celiac disease, giardiasis and idiopathic secretory diarrhea.[1] Small bowel bacterial overgrowth (SBO) is a well-known cause of malabsorption and steatorrhea that is classically described with either a structural abnormality in the small intestine such as jejunal diverticula, surgical blind loop or severe motility disturbance (e.g. ideopathic pseudo-obstruction, diabetic autonomic neuropathy, scleroderma).[2] It is now increasingly recognized that SBO can also present with less specific and severe symptoms without any structural abnormality.[3] For example, it is now appreciated that SBO may be commonly present in the elderly who may have a motility disturbance,[4,5] and in medical conditions such as chronic pancreatitis, chronic renal failure and cirrhosis of the liver.[6,7,8] Symptoms include chronic diarrhea, bloating, flatulence, abdominal pain and nausea.[3]

In SBO, the microbial population resembles that of colonic flora. In health, the proximal small bowel has only few numbers (approximately 103 organisms/mL) of mainly Gram-positive aerobic organisms,[9,10] but excessive numbers of Gram-negative aerobes and anaerobes colonize in SBO.[2] These excess bacteria classically produce diarrhea and malabsorption by deconjugating bile acids, making them inadequate for miceller formation and fat digestion, and so there may not be any villous atrophy present.[1] Other proposed mechanisms of diarrhea are bacterial-induced B12 deficiency, osmolar diarrhea from organic acids produced by bacteria, other bacterial metabolites such as free bile acids, hydroxylated fatty acids and organic acids producing a secretory diarrhea, direct carbodydrate malabsorption and secondary motility disturbance.[11] They can, however, cause diarrhea in severe and protracted overgrowth by inducing additional damage to mucosal enterocytes but this is usually associated with a structural abnormality of the intestine.[2] All these multiple mechanisms lead to carbohydrate, fat, protein and vitamin malaborption. A previous study showed SBO in less than 11% of cases of chronic diarrhea.[12] The true prevalence of SBO as a cause of otherwise obscure chronic diarrhea is unknown and probably underdiagnosed. Often in general practice, patients with chronic diarrhea are treated empirically with antibiotics for presumed giardiasis with improvement of symptoms. Some of these patients may have SBO.

Small bowel bacterial overgrowth remains difficult to diagnose. One method is culture of duodenal fluid with a demonstration of more than 105 c.f.u./mL being diagnostic of SBO. This method has traditionally been regarded as the most accurate method for diagnosing SBO.[1,2] Another method is non-invasive breath sampling of expired products of ingested substrates.[2] The first such test used 14C-glycocholic acid as the substrate but this was insensitive due to a high signal from colonic catabolism.[7] Other substrates that have been used include 14C-xylose,[13] and unlabeled lactulose and glucose.[14,15] All these tests have not been accepted widely due to possible problems with low sensitivity and specificity, but more particularly due to the labor-intensive need of frequent breath sampling.[2] An old observation that could possibly be used to diagnose SBO is an elevated serum folate level.[15,16] This has not previously been evaluated as a possible diagnostic tool. Other measures of quantification such as urinary indican, phenols, drug metabolites and conjugated para-aminobenzoic acid have not been helpful.[3]

In the first part of the present study, we conducted a prospective investigation of the causes of chronic diarrhea. In the second part of the study, the prevalence of SBO in otherwise obscure chronic diarrhea was investigated using duodenal fluid culture and a 14C-D-xylose/lactulose breath test. We incorporated lactulose to detect possible early colonic transit to improve the specificity of the breath test. A group of patients with symptoms of reflux oesophagitis were used as control subjects. The clinical utility of a raised serum folate or red blood cell folate level for the diagnosis of SBO was also tested.

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