Small intestinal bacterial overgrowth

Signs and symptoms

SIBO produces a range of symptoms that overlap with other conditions, complicating diagnosis. Many arise from malabsorption due to bacterial metabolism of nutrients or inflammation of the small bowel. Common symptoms include nausea, flatus, constipation, bloating, abdominal distension, abdominal pain or discomfort, diarrhea, fatigue, and weakness.

Increased permeability of the small intestine occurs. Some patients experience weight loss, and children may develop malnutrition with impaired growth. Steatorrhea, a fatty diarrhea from fat malabsorption, can appear. Long-standing SIBO may lead to complications from nutrient malabsorption.

Blood tests can show elevated folate and, less often, vitamin B12 deficiency or other nutritional deficits; the combination of high folate and low B12 is unusual. Anemia may develop through various mechanisms. Iron malabsorption in the duodenum and jejunum can cause microcytic anemia with small red blood cells, while vitamin B12 malabsorption in the ileum can produce megaloblastic anemia with large red blood cells.

Causes

Certain risk factors predispose individuals to SIBO, grouped into four categories: motility disorders or anatomical changes causing stasis; immune system disorders; interference with proteolytic enzymes, gastric acid, or bile; and conditions that allow more bacteria from the colon to enter the small bowel. Impairment of the migrating motor complex (MMC), especially phase III, is linked to SIBO development. MMC impairment can result from post-infectious IBS, drug use, or intestinal pseudo-obstruction.

There is overlap among tropical sprue, post-infectious IBS, and SIBO in pathophysiology, and SIBO can be triggered by an acute gastrointestinal infection. Controversy remains about SIBO's role in common functional symptoms such as those in IBS. Diseases like scleroderma cause diffuse bowel slowing, raising bacterial concentrations. Anatomical problems such as diverticula can accumulate bacteria.

After stomach or duodenal surgery, particularly Billroth II antrectomy, a blind loop may form, causing stasis and overgrowth (blind loop syndrome). Systemic disorders like diabetes can cause intestinal neuropathy; pancreatitis can impair digestive enzyme production; cirrhosis can affect bile. Use of proton pump inhibitors is associated with increased SIBO risk.

Diagnosis

Malabsorption can be detected via the D-xylose absorption test, where a patient drinks D-xylose and levels are measured in urine and blood; absence suggests poor small bowel absorption rather than enzyme problems. The gold standard for SIBO detection is aspiration and culture of jejunal fluid, with more than 105 colony-forming units per milliliter indicating SIBO. The normal small bowel has fewer than 104 bacteria per milliliter. Some experts consider aspiration of more than 103 positive if the flora is predominantly colonic-type bacteria, as these are pathological in excess.

Reliability of aspiration is questioned because SIBO can be patchy, with reproducibility as low as 38%. Some clinicians factor in response to treatment as part of diagnosis. Breath tests are based on bacterial metabolism of carbohydrates to hydrogen, methane, or hydrogen sulfide, or on detection of by-products of carbohydrate digestion.

The hydrogen breath test involves fasting for at least 12 hours, then drinking glucose or lactulose, and measuring exhaled hydrogen and methane over several hours; it compares well to jejunal aspirates. Carbon-13 and carbon-14 tests use bacterial metabolism of D-xylose. The glycocholic acid breath test administers 14C glycocholic acid and detects elevated 14CO2. Breath tests can be imperfect: methanogens in the mouth may affect results, and they give multiple false positives, but they are commonly used because they are noninvasive and inexpensive.

Treatment

Treatment strategies aim to identify and correct root causes, resolve nutritional deficiencies, and administer antibiotics. Whether antibiotics should be first-line is debated; some experts recommend probiotics first, with antibiotics reserved for more severe cases. Prokinetic drugs are another option, but human research is limited. Various antibiotics have been used, including tetracycline, amoxicillin-clavulanate, metronidazole, neomycin, cephalexin, and trimethoprim-sulfamethoxazole, but the best evidence is for rifaximin, a poorly absorbed antibiotic.

Limited evidence exists on antibiotic effectiveness in SIBO, and randomized controlled trials are still needed. A one-week antibiotic course is usually sufficient; if recurrence occurs, antibiotics can be given cyclically (e.g., one week on, three weeks off) or the antibiotic choice can be cycled to prevent tolerance. Data guiding antibiotic strategies remain limited, and therapy is largely empiric. Concerns exist about long-term broad-spectrum antibiotic risks.

Probiotics alter bowel flora for beneficial effect; animal research shows barrier-enhancing, antibacterial, immune-modulating, and anti-inflammatory effects. Lactobacillus casei improved breath hydrogen scores after six weeks. Lactobacillus plantarum, Lactobacillus acidophilus, and Lactobacillus casei have shown effectiveness, while Lactobacillus fermentum and Saccharomyces boulardii were ineffective. A combination of Lactobacillus plantarum and Lactobacillus rhamnosus suppresses abnormal gas-producing organisms in the small intestine.

Did You Know?

• As of 2020, the definition of SIBO as a clinical entity lacks precision and consistency.
• The main obstacle to accurately defining SIBO is limited understanding of the normal intestinal microbial population.