Sandbox:Mazia

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 were 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

• [Disease name] may be classified according to [classification method] into [number] subtypes/groups:

• [group1]
• [group2]
• [group3]

• Other variants of [disease name] include [disease subtype 1], [disease subtype 2], and [disease subtype 3].

Pathophysiology

• The pathogenesis of small intestinal bacterial overgrowth (SIBO) is characterized by increased microbial load in the small intestine.

[feature2], and [feature3].

• The [gene name] gene/Mutation in [gene name] has been associated with the development of [disease name], involving the [molecular pathway] pathway.
• On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
• On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

SIBO is usually associated with abnormally high counts of multiple organisms in the small intestine. Common species associated with SIBO include streptococci, Bacteroides, Escherichia, and Lactobacillus [12]. Inflammation is caused by invasive strains of bacteria [11]. Facultative anaerobes can injure the intestinal surface by direct adherence and production of enterotoxins. Aerobic bacteria produce enzymes and metabolic products that can induce epithelial cell injury [13].

●Intestinal effects — SIBO can cause maldigestion in the intestinal lumen, or malabsorption at the level of the intestinal microvillus membrane due to enterocyte damage. Bacterial overgrowth can also alter small bowel motility [14].

•Carbohydrate malabsorption – Intraluminal degradation of carbohydrates leads to the production of short-chain fatty acids (butyrate, propionate, acetate, lactate) as well as carbon dioxide, hydrogen, and methane. Enterocyte damage due to bile acids and bacteria results in diarrhea due to reduction in enterocyte disaccharidase activity and transport of monosaccharides [15]. Fermentation of unabsorbed carbohydrates results in bloating, distension, and flatulence.

•Fat malabsorption – Fat malabsorption can lead to steatorrhea, weight loss, and deficiencies of fat-soluble vitamins (eg, vitamin A and D). SIBO results in deconjugation of primary bile acids [16,17]. At physiologic pH, bile acids are fully ionized, preventing their absorption in the proximal small intestine and permitting sufficient concentrations for solubilization of dietary fat. However, deconjugated bile salts are reabsorbed by the jejunum, which may lead to fat malabsorption due to depletion of the normal bile acid pool. Bacterial deconjugation also leads to the production of lithocholic acid, which may be toxic to intestinal epithelium, resulting in impaired absorption of fat and other nutrients. Hydroxylated fatty acids (and free bile acids) also stimulate the secretion of water and electrolytes, leading to diarrhea. (See 'Clinical features' below.)

•Protein malabsorption – Protein malabsorption results from damage to the epithelial barrier, resulting in increased intestinal permeability, decreased mucosal uptake of amino acids, and the intraluminal degradation of protein precursors by bacteria [18]. SIBO can also result in a reversible form of protein-losing enteropathy [19]. (See "Protein-losing gastroenteropathy".)

•Vitamin deficiency and excess – Vitamin B12 deficiency in SIBO result from several different mechanisms. Although enteric bacteria synthesize cobalamin, they also successfully compete with the host for its absorption. In patients with severe SIBO, malabsorption of vitamin B12 results from mucosal damage to the ileal binding site. Only anaerobes can utilize vitamin B12 coupled to intrinsic factor. Thiamine and nicotinamide deficiency also result from bacterial utilization.

In contrast, folate and vitamin K levels are elevated in SIBO due to bacterial synthesis. Increased intestinal permeability also contributes to increased vitamin K levels.

●Systemic effects — Production of toxins and increased intestinal permeability in SIBO have been associated with systemic complications. D-lactic acidosis is a rare neurologic syndrome in patients with SIBO associated with short bowel syndrome or a prior jejunoileal bypass. It is characterized by altered mental status ranging from confusion to coma, slurred speech, seizures, and ataxia resulting from bacterial fermentation of unabsorbed carbohydrates [20]. (See "D-lactic acidosis", section on 'Pathogenesis' and 'Clinical features' below.)

Bacterial overgrowth has also been implicated in the pathogenesis of hepatic encephalopathy and nonalcoholic fatty liver disease. (See "Pathogenesis of nonalcoholic fatty liver disease", section on 'Intestinal microbes' and "Hepatic encephalopathy: Pathogenesis", section on 'Bacterial overgrowth'.)

Causes

• [Disease name] may be caused by either [cause1], [cause2], or [cause3].
• [Disease name] is caused by a mutation in the [gene1], [gene2], or [gene3] gene[s].
• There are no established causes for [disease name].

Differentiating [disease name] from other Diseases

• [Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as:

• [Differential dx1]
• [Differential dx2]
• [Differential dx3]

Epidemiology and Demographics

• The prevalence of SIBO is unknown.
• In [year], the incidence of [disease name] was estimated to be [number or range] cases per 100,000 individuals in [location].

Age

• Patients of all age groups may develop [disease name].

• [Disease name] is more commonly observed among patients aged [age range] years old.
• Small intestinal bacterial overgrowth is more commonly observed among elderly patients.

Gender

• [Disease name] affects men and women equally.

• [Gender 1] are more commonly affected with [disease name] than [gender 2].
• The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.

Race

• There is no racial predilection for [disease name].

• [Disease name] usually affects individuals of the [race 1] race.
• [Race 2] individuals are less likely to develop [disease name].

The prevalence of SIBO in the general population is unknown but estimated to be 0–35% in healthy individuals.9

Anywhere from 30% to 85% of adult

patients with IBS are estimated to have SIBO,9-11 with the most current data reporting 67% as determined by duodenal aspiration and culture.6

Two meta-analyses

have shown 3.5–9.6-fold increased odds of SIBO in patients with IBS.12 In the United States and Europe, one in five school-aged children have been diagnosed with abdominal pain-related functional gastrointestinal disorders, including IBS and functional abdominal pain; SIBO has been shown to occur in 34% of pediatric IBS patients.10 A 2015 study demonstrated that 63% of children aged 4–17 years who were hospitalized for abdominal pain had SIBO.13 Elderly patients may be particularly susceptible to SIBO due to a lack of gastric acid and the use of medications that slow gastrointestinal transit.9

SIBO prevalence may

be as high as 15% in the elderly and is an important cause of unexplained diarrhea in this population.12,14 SIBO also is common in patients with liver cirrhosis (50%), celiac disease (50%)9

and gastroparesis (39%).15

Risk Factors

• Common risk factors in the development of [disease name] are [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].

Natural History, Complications and Prognosis

• The majority of patients with [disease name] remain asymptomatic for [duration/years].
• Early clinical features include [manifestation 1], [manifestation 2], and [manifestation 3].
• If left untreated, [#%] of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
• Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
• Prognosis is generally [excellent/good/poor], and the [1/5/10­year mortality/survival rate] of patients with [disease name] is approximately [#%].

Diagnosis

Diagnostic Criteria

• The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met:

• [criterion 1]
• [criterion 2]
• [criterion 3]
• [criterion 4]

Symptoms

• [Disease name] is usually asymptomatic.
• Symptoms of [disease name] may include the following:

• [symptom 1]
• [symptom 2]
• [symptom 3]
• [symptom 4]
• [symptom 5]
• [symptom 6]

Physical Examination

• Patients with [disease name] usually appear [general appearance].
• Physical examination may be remarkable for:

• [finding 1]
• [finding 2]
• [finding 3]
• [finding 4]
• [finding 5]
• [finding 6]

Laboratory Findings

• There are no specific laboratory findings associated with [disease name].

• A [positive/negative] [test name] is diagnostic of [disease name].
• An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
• Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].

Imaging Findings

• There are no [imaging study] findings associated with [disease name].

• [Imaging study 1] is the imaging modality of choice for [disease name].
• On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
• [Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].

Other Diagnostic Studies

• [Disease name] may also be diagnosed using [diagnostic study name].
• Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

Treatment

Medical Therapy

• There is no treatment for [disease name]; the mainstay of therapy is supportive care.

• The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
• [Medical therapy 1] acts by [mechanism of action 1].
• Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].

Surgery

• Surgery is the mainstay of therapy for [disease name].
• [Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
• [Surgical procedure] can only be performed for patients with [disease stage] [disease name].

Prevention

• There are no primary preventive measures available for [disease name].

• Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].

• Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].