Small intestinal bacterial overgrowth syndrome
Synonyms and keywords:SIBO; small bowel bacterial overgrowth.

# Overview
Small intestinal bacterial overgrowth (SIBO) was first discovered by Barber and Hummel in 1939. There is no established system for the classification of small intestinal bacterial overgrowth (SIBO).The pathogenesis of small intestinal bacterial overgrowth (SIBO) is characterized by an increased microbial load in the small intestine. Disruption of protective homeostatic mechanisms can increase the risk of SIBO. Bacterial colonization causes an inflammatory response in the intestinal mucosa. Damage to the intestinal mucosa leads to malabsorption of bile acids, carbohydrates, proteins and vitamins resulting in symptoms of diarrhea and weight loss. On gross pathology, mucosal edema, loss of normal vascular pattern, patchy erythema, friability and ulceration of the small intestinal wall is associated with small intestinal bacterial overgrowth (SIBO). On microscopic histopathological analysis small intestine and colon are normal in most patients with SIBO. Findings include blunting of the intestinal villi, thinning of the mucosa and crypts, increased intraepithelial lymphocytes. Small intestinal bacterial overgrowth (SIBO) must be differentiated from other diseases that cause chronic diarrhea. Small intestinal bacterial overgrowth is more commonly observed among elderly patients. Small intestinal bacterial overgrowth (SIBO) affects men and women equally.There is no racial predilection for small intestinal bacterial overgrowth (SIBO). Early clinical features include bloating, flatulence, abdominal pain. If left untreated, patients with small intestinal bacterial overgrowth (SIBO) may progress to develop diarrhea, dyspepsia and weight loss. Prognosis is generally good and associated with frequent relapses and symptom-free periods. The diagnosis of small intestinal bacterial overgrowth (SIBO) is made when at least one of the following diagnostic criteria are met: a positive carbohydrate breath test or bacterial concentration of >103 units/mL in a jejunal aspirate culture. Physical examination may be remarkable for distended abdomen with positive succussion splash as a result of distended bowel loops and peripheral edema due to malabsorption. Small intestinal bacterial obstruction(SIBO) may also be diagnosed using breath tests. The mainstay of therapy for small intestinal bacterial overgrowth (SIBO) is antibiotic therapy. Surgical approach can only be performed for patients with strictures, fistulae, and diverticula or any other structural abnormality resulting in obstruction and resultant bacterial overgrowth. Effective measures for the prevention of small bowel bacterial overgrowth syndrome include avoiding medications like narcotics and benzodiazepines that decrease intestinal motility and avoid achlorhydria in high-risk patients. Consider antibiotic prophylaxis for patients with four or more episodes of recurrent small bowel bacterial overgrowth syndrome within one year.

# Historical Perspective
- Small intestinal bacterial overgrowth (SIBO) was first discovered by  Barber and Hummel in 1939.
- In 2000, Pimentel et all at Cedars-Sinai Medical Center first identified that SIBO was present in 78% of patients with irritable bowel syndrome (IBS), and that treatment with antibiotics improved symptoms.
- In May 2015,  U.S. Food and Drug Administration (FDA) approved rifaximin to treat SIBO.

# Classification
- There is no established system for the classification of small intestinal bacterial overgrowth (SIBO).

# Pathophysiology
- The pathogenesis of small intestinal bacterial overgrowth (SIBO) is characterized by an increased microbial load in the small intestine.
- A healthy individual has less than 103 organisms/mL in the upper small intestine and the majority of these organisms are gram-positive bacteria.
- Human body's homeostatic mechanisms that protect against excessive small intestinal colonization by bacteria include :
Gastric acid and bile eradicate micro-organisms before they leave the stomach.
Migrating motor complex clears the excess  bacteria of upper intestine.
Intestinal mucosa serves as a protective layer for the gut wall.
Normal intestinal flora (eg, Lactobacillus) maintains a low pH that prevents bacterial overgrowth.
Physical barrier of the ileocecal valve that prevents retrograde translocation of bacteria from colon to the small intestine.
- Gastric acid and bile eradicate micro-organisms before they leave the stomach.
- Migrating motor complex clears the excess  bacteria of upper intestine.
- Intestinal mucosa serves as a protective layer for the gut wall.
- Normal intestinal flora (eg, Lactobacillus) maintains a low pH that prevents bacterial overgrowth.
- Physical barrier of the ileocecal valve that prevents retrograde translocation of bacteria from colon to the small intestine.
- Disruption of these protective homeostatic mechanisms can increase the risk of SIBO.
- Bacterial colonization causes an inflammatory response in the intestinal mucosa.
- Damage to the intestinal mucosa leads to malabsorption of bile acids, carbohydrates, proteins, and vitamins resulting in symptoms of diarrhea and weight loss.
- On gross pathology, mucosal edema, loss of normal vascular pattern, patchy erythema, friability and ulceration of the small intestinal wall is associated with small intestinal bacterial overgrowth (SIBO).
- On microscopic histopathological analysis small intestine and colon is normal in most patients with SIBO. However, in some patients, findings may include:
Blunting of the intestinal villi
Thinning of the mucosa and crypts
Increased intraepithelial lymphocytes
- Blunting of the intestinal villi
- Thinning of the mucosa and crypts
- Increased intraepithelial lymphocytes

# Causes
- Small intestinal bacterial overgrowth (SIBO) may be caused by disruption of the protective homeostatic mechanisms that control enteric bacteria population.
- Causes of small intestinal bacterial overgrowth (SIBO) include:
Irregular small intestinal motility:
Diabetic autonomic neuropathy
Scleroderma
Pseudo-obstruction
Amyloidosis
Neurological diseases (eg, myotonic dystrophy, Parkinson disease)
Radiation enteritis
Crohn disease
Hypothyroidism
Blind pouches in the gastrointestinal tract:
Side-to-side or end-to-side anastomoses
Duodenal or jejunal diverticula
Segmental dilatation of the ileum
Blind loop syndrome
Biliopancreatic diversion
Chagasic megacolon
Fistula:
Gastrocolic fistulae
Jejunal-colic fistulae
Partial Obstruction:
Strictures
Adhesions
Abdominal masses
Leiomyosarcoma
Decreased gastric acid secretion:
Achlorhydria
Vagotomy
Long-term proton pump inhibitor therapy
- Irregular small intestinal motility:
Diabetic autonomic neuropathy
Scleroderma
Pseudo-obstruction
Amyloidosis
Neurological diseases (eg, myotonic dystrophy, Parkinson disease)
Radiation enteritis
Crohn disease
Hypothyroidism
- Diabetic autonomic neuropathy
- Scleroderma
- Pseudo-obstruction
- Amyloidosis
- Neurological diseases (eg, myotonic dystrophy, Parkinson disease)
- Radiation enteritis
- Crohn disease
- Hypothyroidism
- Blind pouches in the gastrointestinal tract:
Side-to-side or end-to-side anastomoses
Duodenal or jejunal diverticula
Segmental dilatation of the ileum
Blind loop syndrome
Biliopancreatic diversion
Chagasic megacolon
- Side-to-side or end-to-side anastomoses
- Duodenal or jejunal diverticula
- Segmental dilatation of the ileum
- Blind loop syndrome
- Biliopancreatic diversion
- Chagasic megacolon
- Fistula:
Gastrocolic fistulae
Jejunal-colic fistulae
- Gastrocolic fistulae
- Jejunal-colic fistulae
- Partial Obstruction:
Strictures
Adhesions
Abdominal masses
Leiomyosarcoma
- Strictures
- Adhesions
- Abdominal masses
- Leiomyosarcoma
- Decreased gastric acid secretion:
Achlorhydria
Vagotomy
Long-term proton pump inhibitor therapy
- Achlorhydria
- Vagotomy
- Long-term proton pump inhibitor therapy

# Differentiating Small Intestinal Bacterial Overgrowth from other Diseases
- Small intestinal bacterial overgrowth (SIBO) must be differentiated from other diseases that cause chronic diarrhea. For differential diagnosis of chronic diarrhoea, click here.

# Epidemiology and Demographics
Epidemiology and demographics of small intestinal bacterial overgrowth is as follows: 

## Age
- Small intestinal bacterial overgrowth is more commonly observed among elderly patients.

## Gender
- Small intestinal bacterial overgrowth (SIBO) affects men and women equally.

## Race
- There is no racial predilection for small intestinal bacterial overgrowth (SIBO).

# Risk Factors
- Common risk factors in the development of small intestinal bacterial overgrowth (SIBO) are :
Intestinal tract surgery
Irritable bowel syndrome
Liver cirrhosis
Celiac disease
Immune deficiency (eg, AIDS, IgA deficiency, severe malnutrition)
Short bowel syndrome
End-stage renal disease
Gastrojejunal anastomosis
Antral resection
Pancreatic exocrine insufficiency
- Intestinal tract surgery
- Irritable bowel syndrome
- Liver cirrhosis
- Celiac disease
- Immune deficiency (eg, AIDS, IgA deficiency, severe malnutrition)
- Short bowel syndrome
- End-stage renal disease
- Gastrojejunal anastomosis
- Antral resection
- Pancreatic exocrine insufficiency

# Natural History, Complications and Prognosis
- Early clinical features include bloating, flatulence, abdominal pain.
- If left untreated, patients with small intestinal bacterial overgrowth (SIBO) may progress to develop diarrhea, dyspepsia and weight loss.
- Common complications of small intestinal bacterial overgrowth (SIBO) include:
Iron deficiency resulting in microcytic anemia
Vitamin B-12 or folate deficiency resulting in macrocytic anemia
Vitamin B-12 deficiency associated polyneuropathy
Steatorrhea
Hypocalcemia
Vitamin A deficiency resulting in night blindness
Selenium deficiency causing dermatitis
Rosacea
Cachexia as a result of protein-energy malnutrition
- Iron deficiency resulting in microcytic anemia
- Vitamin B-12 or folate deficiency resulting in macrocytic anemia
- Vitamin B-12 deficiency associated polyneuropathy
- Steatorrhea
- Hypocalcemia
- Vitamin A deficiency resulting in night blindness
- Selenium deficiency causing dermatitis
- Rosacea
- Cachexia as a result of protein-energy malnutrition
- Prognosis is generally good and associated with frequent relapses and symptom-free periods.

# Diagnosis

## Diagnostic Criteria
Clinical practice guidelines by the American College of Gastroenterology guide diagnosis.
- The diagnosis of small intestinal bacterial overgrowth (SIBO) is made when at least one of the following diagnostic criteria are met:
A positive carbohydrate breath test with an increase in hydrogen concentrations of 20 ppm from baseline within 90 - 120 minutes.
Bacterial concentration of >= 103 colony-forming units per milliliter (CFU/mL) in a duodenal/jejunal aspirate
- A positive carbohydrate breath test with an increase in hydrogen concentrations of 20 ppm from baseline within 90 - 120 minutes.
- Bacterial concentration of >= 103 colony-forming units per milliliter (CFU/mL) in a duodenal/jejunal aspirate

## Symptoms
- Symptoms of small intestinal bacterial overdose (SIBO) may include the following:
- Bloating
- Flatulence
- Abdominal discomfort
- Chronic watery diarrhea
- Weight loss

## Physical Examination
- Patients with small intestinal bacterial overgrowth (SIBO) usually appear normal.
- Physical examination may be remarkable for:
- Distended abdomen with positive succussion splash as a result of distended bowel loops
- Peripheral edema due to malabsorption

## Laboratory Findings
- A  positive carbohydrate breath test has a sensitivity of 55% and specificity of 82%  of small intestinal bacterial overgrowth (SIBO).
- An elevated concentration of bacterial colony forming units >103/mL in jejunal aspirate culture is diagnostic of small intestinal bacterial overgrowth (SIBO).
- Other laboratory findings consistent with the diagnosis of small intestinal bacterial overgrowth (SIBO) include:
Macrocytic anemia
B12 deficiency
Presence of fecal fat on stool examination.
Low levels of thiamine and niacin
Elevated serum folate and vitamin K levels
- Macrocytic anemia
- B12 deficiency
- Presence of fecal fat on stool examination.
- Low levels of thiamine and niacin
- Elevated serum folate and vitamin K levels

## Imaging Findings
- The CT abdomen or MRI may demonstrate associated strictures, malrotation, fistulae.
- Small intestinal bacterial overgrowth can result in small bowel obstruction that presents as small bowel feces sign on abdominal CT.
- Small bowel feces sign is the presence of particulate feculent material mingled with gas bubbles in the lumen of the small intestine, it is believed to be the result of delayed intestinal transit.

## Other Diagnostic Studies

### Breath Tests
- Small intestinal bacterial obstruction (SIBO) may also be diagnosed using breath tests.
- Breath tests have the advantage of being easy to perform, noninvasive, and inexpensive. Breath tests are based on the principle that carbohydrates are metabolized by bacteria in the gut to produce hydrogen or methane that is absorbed and excreted in breath.
- The findings on carbohydrate breath test diagnostic of small intestinal bacterial obstruction (SIBO) include:
An increase in hydrogen by 20 ppm above baseline within 90 minutes.
A methane level 10 ppm regardless of the time during the breath test.
- An increase in hydrogen by 20 ppm above baseline within 90 minutes.
- A methane level 10 ppm regardless of the time during the breath test.
Preparation for breath testing
Indications for the patient
- Fasting period prior to test should be 8-12 h
- Antibiotics should be avoided 4 weeks prior to test
- Prokinetic agents (e.g. cisapride, domperidone, erythromycin) and laxatives should be stopped 1 week prior to testif tolerated by the patient
- Complex carbohydrates (e.g. bread, pasta, rice, legumes, etc.) should be avoided 24 hours prior to test
- Physical activity should be avoided during the test
- Smoking should be avoided on the day of the test
- It is not necessary to stop proton pump inhibitors for the test
Indications for the physician
- Lactulose dose: 10 g followed by one cup of water
- Glucose dose: 75 g mixed with or followed by one cup of water
- Lactose: 25 g mixed with one cup of water
- Fructose: 25 g mixed with or followed by one cup of water

# Treatment
Treatment options available for small intestinal bacterial overgrowth syndrome are as follows: 

## Medical Therapy
- The mainstay of therapy for small intestinal bacterial overgrowth (SIBO) is antibiotic therapy.
- Antibiotics acts by eliminating the bacterial overgrowth.
- Rifaximin is the antibiotic of choice for the treatment of small intestinal bacterial overgrowth (SIBO).
Rifaximin may only work in patients who have irritable bowel syndrome
Preferred regimen: Rifaximin 550 mg PO q8h for 14 days.
- Rifaximin may only work in patients who have irritable bowel syndrome
- Preferred regimen: Rifaximin 550 mg PO q8h for 14 days.
- Response to antibiotics can be assessed by the symptomatic improvement. In case of recurrent symptoms, the antibiotic dose is repeated.

## Surgery
- Surgical approach can only be performed for patients with strictures, fistulae, and diverticula or any other structural abnormality resulting in obstruction and resultant bacterial overgrowth.

## Prevention
- Effective measures for the prevention of small bowel bacterial overgrowth syndrome include:
Avoiding medications like narcotics and benzodiazepines that decrease intestinal motility.
Avoid achlorhydria in high-risk patients.
Consider antibiotic prophylaxis for patients with four or more episodes of recurrent small bowel bacterial overgrowth syndrome within one year.
- Avoiding medications like narcotics and benzodiazepines that decrease intestinal motility.
- Avoid achlorhydria in high-risk patients.
- Consider antibiotic prophylaxis for patients with four or more episodes of recurrent small bowel bacterial overgrowth syndrome within one year.