TABLE 16. Etiology of the bacterial overgrowth syndrome

Breakdown of normal defense mechanisms
Achlorhydria
Stasis:

• Anatomic (Crohn's disease, diverticula, lymphoma, strictures)
  
• Functional (scleroderma, diabetic autonomic neuropathy, pseudo-obstruction)

Contamination
Postinfection
Enteroenteric fistulas, gastrocolic fistulas

Steatorrhea results from the deconjugation and dehydroxylation of bile acids; lithocholic acid is precipitated and free bile acids are reabsorbed passively, making them unavailable and incapable of performing micellar solubilization. There may also be mucosal damage. Fats, cholesterol and fat-soluble vitamins are malabsorbed. Vitamin B₁₂ is also malabsorbed as a result of the binding and incorporation of this vitamin into the bacteria. Folate deficiency, however, is not a common occurrence in bacterial overgrowth; unlike vitamin B₁₂, folate synthesized by microorganisms in the small bowel is available for host absorption. In patients with small bowel bacterial overgrowth, serum folate levels tend to be high rather than low. The enteric bacteria also produce vitamin K, and patients with bacterial overgrowth who are on the anticoagulant warfarin may have difficulty in maintaining the desired level of anticoagulation. In addition to steatorrhea, patients with bacterial overgrowth frequently complain of watery diarrhea. Important mechanisms in producing this diarrhea include (1) disturbances of the intraluminal environment with deconjugated bile acids, and hydroxylated fatty and organic acids; and (2) direct changes in gut motility.

In some patients, symptoms of the primary disease predominate, and evidence of bacterial overgrowth may be found only on investigation. In others, the primary condition is symptomless, and the patient presents with a typical malabsorption syndrome due to bacterial overgrowth (Table 17).

TABLE 17.  Diagnosis of the bacterial overgrowth syndrome

Jejunal culture

Tests of bile salt deconjugation
¹⁴C-glycocholate breath tests
In vitro deconjugation assessment

Tests of malassimilation
Vitamin B₁₂ (Schilling test)
D-xylose, glucose, lactulose
H₂ breath tests

Once diagnosis of bacterial overgrowth is suspected a careful history should be performed to identify possible causes. Physical examination may be normal or may demonstrate signs related to specific nutrient deficiencies.

A small bowel biopsy is of value in excluding primary mucosal disease as the cause of the malabsorption. Histologic abnormalities of the jejunal mucosa are usually not seen in patients with bacterial overgrowth. The sine qua non for the diagnosis of bacterial overgrowth is a properly collected and appropriately cultured aspirate of the proximal small intestine. Specimens should be obtained under anaerobic conditions and quantitative colony counts determined. Generally, bacteria concentrations of greater than 10⁵ organisms per mL are highly suggestive of bacterial overgrowth. Such methods are difficult and usually undertaken only in a research setting. Alternatively, one can attempt to demonstrate a metabolic effect of the bacterial overgrowth, such as intraluminal bile acid deconjugation by the bile acid or ¹⁴C-glycocholate breath test. Cholylglycine-¹⁴C (glycine-conjugated cholic acid with the radiolabeled ¹⁴C on the glycine moiety) when ingested circulates normally in the enterohepatic circulation without deconjugation. Bacterial overgrowth within the small intestine splits the ¹⁴C-labeled glycine moiety and subsequently oxidizes it to ¹⁴C-labeled CO₂, which is absorbed in the intestine and exhaled. Excess ¹⁴CO₂ appears in the breath. The bile acid breath test cannot differentiate bacterial overgrowth from ileal damage or resection where excessive breath ¹⁴CO₂ production is due to bacterial deconjugation within the colon of unabsorbed ¹⁴C-labeled glycocholate. This creates clinical difficulties, since bacterial overgrowth may be superimposed on ileal damage in such conditions as Crohn's disease.

Breath hydrogen analysis allows a distinct separation of metabolic activity of intestinal flora of the host, since no hydrogen production is known to occur in mammalian tissue. Excessive and early breath hydrogen production has been noted in patients with bacterial overgrowth following the oral administration of either 50 g of glucose or 10 g of lactulose.

Another hallmark of bacterial overgrowth is steatorrhea, detected by the 72-hour fecal fat collection.

The Schilling test also is abnormal. ⁵⁷Co-B₁₂ is given with intrinsic factor following a flushing dose of nonradioactive B₁₂ given parenterally to prevent tissue storage of the labeled vitamin. In healthy subjects, ⁵⁷Co-B₁₂ combines with intrinsic factor and is absorbed and >8% excreted in the urine within 24 hours. In patients with bacterial overgrowth, the bacteria combine with or destroy intrinsic factor, the vitamin or both, causing decreased vitamin B₁₂ absorption. Following treatment with antibiotics the B₁₂ absorption returns to normal.