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.
• A healthy individual has less than 103 organisms/mL in the upper small intestine, and the majority of these organisms are gram-positive bacteria.

[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].

Normally, colony counts of gram-positive bacteria and fungi in the duodenum and jejunum are less than 1X105 organisms/mL. Anaerobic bacteria are not found in the jejunum in healthy people. As many as one third of jejunal aspirates may be sterile in healthy people. Aerobic and anaerobic bacterial colony counts in the ileum are usually less than 1 X 108 organisms/mL. This is in sharp contrast to the 1 X 1011 organisms/mL that colonize the colon. Prevalence of bacteria in different parts of GI tract depends on several factors such as peristalsis, pH, redox potential, bacterial adhesion, bacterial cooperation and antagonism, mucin secretion, diet, and nutrient availability. [1]

Studies of duodenal aspirates have not identified any particular bacteria as a cause of bacterial overgrowth syndrome. However, 1 X 1011 organisms/mL of aspirate fluid is diagnostic for bacterial overgrowth syndrome. Cultures grown from patients with bacterial overgrowth syndrome reveal abnormally large numbers of anaerobic bacteria in addition to normal flora.

Several protective factors stabilize the number and type of bacteria that colonize the upper GI tract. Abnormalities in these mechanisms predispose to bacterial overgrowth.

Two coordinated motor phenomena produce the continuous propulsive peristaltic action of the upper GI tract. Both the migrating motor complex and the migrating action potential complex clear the upper intestine of unwanted bacteria and undigested substances. Desynchronization of these complexes results in diarrhea and weight loss in animal models. Anatomical defects can reduce peristaltic efficacy; for example, blind pouches result in a stagnant portion of the intestine.

Gastric acid and bile destroy many micro-organisms before they leave the stomach.

Enzymatic activity of intestinal, pancreatic, and biliary secretions help destroy bacteria in the small intestine. [2]

The bowel mucosal integrity and mucin layer protect the gut from bacteria.

Immunoglobulin secretion and immune cells (eg, macrophages and lymphocytes) protect the gut from bacteria.

Normal intestinal flora (eg, Lactobacillus) protects the gut from bacterial overgrowth by maintaining a low pH; however, normal flora can facilitate an abnormal intraluminal environment. Abnormal communications produce pathways that allow enteric bacteria to pass between the proximal and distal bowel.

Ileocecal valve prevents retrograde translocation of bacteria from colon to the small intestine. [2]

Malabsorption of bile acids, fats, carbohydrates, proteins, and vitamins results in direct damage to the lining of the luminal surface by bacteria or by transformation of nutrients into toxic metabolites, leading to many of the symptoms of diarrhea and weight loss associated with bacterial overgrowth syndrome. This leads to decreased function of the enterocytes within the intestinal lining and subsequent malabsorption. Diarrhea is potentiated by unabsorbed food products stimulating secretory cells within the colon.

Anaerobes such as Bacteroides fragilis actively deconjugate bile acids, thereby preventing proper bile acid function and enterohepatic circulation.

Fatty acid absorption is reduced because deconjugated bile acids cannot form micelles.

Deconjugated bile acids directly inhibit carbohydrate transporters. These unabsorbed sugars ferment into organic acids, thereby reducing the intraluminal pH and producing osmotic diarrhea. The unconjugated bile acids also damage intestinal enterocytes and induce water secretion by the colonic mucosa.

Loss of bile acids in the stool reduces the bile acid pool.

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].