Small bowel bacterial overgrowth syndrome

Small bowel bacterial overgrowth syndrome (SBBOS), or small intestinal bacterial overgrowth (SIBO), also termed bacterial overgrowth; is a disorder of excessive bacterial growth in the small intestine. Unlike the colon (or large bowel), which is rich with bacteria, the small bowel usually has less than 10⁴ organisms per millilitre.^[1] Patients with bacterial overgrowth typically develop symptoms including nausea, bloating, vomiting and diarrhea, which is caused by a number of mechanisms. The diagnosis of bacterial overgrowth is made by a number of techniques, with the gold standard diagnosis being an aspirate from the jejunum that grows in excess of 10⁵ bacteria per millilitre. Risk factors for the development of bacterial overgrowth include the use of medications including proton pump inhibitors, anatomical disturbances in the bowel, including fistulae, diverticula and blind loops created after surgery, and resection of the ileo-cecal valve. Small bowel bacterial overgrowth syndrome is treated with antibiotics, which may be given in a cyclic fashion to prevent tolerance to the antibiotics.

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Clinical presentation

  Bacterial overgrowth can cause a variety of symptoms, many of which are also found in other conditions, making the diagnosis challenging at times.^[1][2] Many of the symptoms are due to malabsorption of nutrients due to the effects of bacteria which either metabolize nutrients or cause inflammation of the small bowel impairing absorption. The symptoms of bacterial overgrowth include nausea, bloating, flatus, and chronic diarrhea. Some patients may develop abdominal discomfort and lose weight. Children with bacterial overgrowth may develop malnutrition have difficulty attaining proper growth. Steatorrhea is a sticky type of diarrhea, where lipids are malabsorbed and spill into the stool.^[3]

Patients with bacterial overgrowth that is longstanding can develop complications of their illness as a result of malabsorption of nutrients. Anemia may occur from a variety of mechanisms, as many of the nutrients involved in production of red blood cells are absorbed in the affected small bowel. Iron is absorbed in the more proximal parts of the small bowel, the duodenum and jejunum, and patients with malabsorption of iron can develop a microcytic anemia, with small red blood cells. Vitamin B12 is absorbed in the last part of the small bowel, the ileum, and patients who malabsorb vitamin B12 can develop a megaloblastic anemia with large red blood cells.^[3]

Pathophysiology

Certain species of bacteria are more commonly found in aspirates of the jejunum taken from patients with bacterial overgrowth. The most common isolates are Escherichia coli, Streptococcus, Lactobacillus, Bacteroides, and Enterococcus species.^[4]

Soon after birth, the gastrointestinal tract is colonized with bacteria, which, on the basis of models with animals raised in a germ-free environment, have beneficial effects on function of the gastrointestinal tract. There are 500-1000 different species of bacteria that reside in the bowel.^[5] However, if the flora of the small bowel is altered, inflammation or altered digestion can occur, leading to symptoms. Many patients with chronic diarrhea have bacterial overgrowth as a cause or a contributor to their symptoms.^[2] While the consensus definition of chronic diarrhea varies, in general it is considered to be an alteration in stool consistency or increased frequency, that occurs for over three weeks. Various mechanisms are involved in the development of diarrhea in bacterial overgrowth. First, the excessive bacterial concentrations can cause direct inflammation of the small bowel cells, leading to an inflammatory diarrhea. The malabsorption of lipids, proteins and carbohydrates may cause poorly digestible products to enter into the colon. This can cause diarrhea by the osmotic drive of these molecules, but can also stimulate the secretory mechanisms of colonic cells, leading to a secretory diarrhea.^[3]

Risk factors and causes

Certain patients are more predisposed to the development of bacterial overgrowth because of certain risk factors. These factors can be grouped into three categories: (1) disordered motility or movement of the small bowel or anatomical changes that lead to stasis, (2) disorders in the immune system and (3) conditions that cause more bacteria from the colon to enter the small bowel.^[1]

Problems with motility may either be diffuse, or localized to particular areas. Diseases like scleroderma^[6] and possibly celiac disease^[7] cause diffuse slowing of the bowel, leading to increased bacterial concentrations. More commonly, the small bowel may have anatomical problems, such as out-pouchings known as diverticula that can cause bacteria to accumulate.^[8] After surgery involving the stomach and duodenum (most commonly with Billroth II antrectomy), a blind loop may be formed, leading to stasis of flow of intestinal contents. This can cause overgrowth, and is termed blind loop syndrome.^[9]

Disorders of the immune system can cause bacterial overgrowth. Chronic pancreatitis, or inflammation of the pancreas can cause bacterial overgrowth through mechanisms linked to this.^[10] The use of immunosuppressant medications to treat other conditions can cause this, as evidenced from animal models.^[11] Other causes include inherited immunodeficiency conditions, such as combined variable immunodeficiency, IgA deficiency, and hypogammaglobulinemia.^[12]

Finally, abnormal connections between the bacteria-rich colon and the small bowel can increase the bacterial load in the small bowel. Patients with Crohn's disease or other diseases of the ileum may require surgery that removes the ileo-cecal valve connecting the small and large bowel; this leads to an increased reflux of bacteria into the small bowel.^[13] After bariatric surgery for obesity, connections between the stomach and the ileum can be formed, which may increase bacterial load in the small bowel.^[14] Proton pump inhibitor medications that decrease acid in the stomach cause bacterial overgrowth by a similar mechanism, as they prevent the anti-bacterial effects of acid in the stomach. The clinical significance of this in causing symptoms is unclear.^[15][16]

Diagnosis

The diagnosis of bacterial overgrowth can be made by physicians in various ways. Malabsorption can be detected by a test called the D-xylose test. Xylose is a sugar that does not require enzymes to be digested. The D-xylose test involves having a patient to drink a certain quantity of D-xylose, and measuring levels in the urine and blood; if there is no evidence of D-xylose in the urine and blood, it suggests that the small bowel is not absorbing properly (as opposed to problems with enzymes required for digestion).^[17]

The gold standard for detection of bacterial overgrowth is the aspiration of more than 10⁵ bacteria per millilitre from the small bowel. The normal small bowel has less than 10⁴ bacteria per millilitre.^[18]

  Breath tests have been developed to test for bacterial overgrowth, based on bacterial metabolism of carbohydrates to hydrogen, or based on the detection of by-products of digestion of carbohydrates that are not usually metabolized. The hydrogen breath test involves giving patients a load of carbohydrate (usually in the form of rice) and measuring expired hydrogen concentrations after a certain time. It compares well to jejunal aspirates in making the diagnosis of bacterial overgrowth.^{[19] 13}C and ¹⁴C based tests have also been developed based on the bacterial metabolism of D-xylose. Increased bacterial concentrations are also involved in the deconjugation of bile acids. The glycocholic acid breath test involves the administration of the bile acid ¹⁴C glychocholic acid, and the detection of ¹⁴CO₂, which would be elevated in bacterial overgrowth.^[20]

Some patients with symptoms of bacterial overgrowth will undergo gastroscopy, or visualization of the stomach and duodenum with an endoscopic camera. Biopsies of the small bowel in bacterial overgrowth can mimic those of celiac disease, making the diagnosis more challenging. Findings include blunting of villi, hyperplasia of crypts and an increased number of lymphocytes in the lamina propria.^[21]

However, some physicians suggest that if the suspicion of bacterial overgrowth is high enough, the best diagnostic test is a trial of treatment. If the symptoms improve, an empiric diagnosis of bacterial overgrowth can be made.^[22]

Treatment

Bacterial overgrowth is usually treated with a course of antibiotics. A variety of antibiotics, including neomycin, rifaximin, amoxicillin-clavulanate, fluoroquinolone antibiotics and tetracycline have been used; however, the best evidence is for the use of norfloxacin and amoxicillin-clavulanate.^[23]

A course of one week of antibiotics is usually sufficient to treat the condition. However, if the condition recurs, antibiotics can be given in a cyclical fashion in order to prevent tolerance. For example, antibiotics may be given for a week, followed by three weeks off antibiotics, followed by another week of treatment. Alternatively, the choice of antibiotic used can be cycled.^[22]

The condition that predisposed the patient to bacterial overgrowth should also be treated. For example, if the bacterial overgrowth is caused by chronic pancreatitis, the patient should be treated with coated pancreatic enzyme supplements.

Probiotics are bacterial preparations that alter the bacterial flora in the bowel to cause a beneficial effect. Their role in bacterial overgrowth is somewhat uncertain.^[1]

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