Small intestinal bacterial overgrowth syndrome

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Small intestinal bacterial overgrowth syndrome
ICD-10 K63
ICD-9 579.9
DiseasesDB 29209
MedlinePlus 000222
eMedicine med/198 

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Overview

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

  • 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.
  • Body's homeostatic mechanisms 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 unwanted 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 weightloss.
  • 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. Findings include:
    • 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

Differentiating [disease name] from other Diseases

  • Small intestinal bacterial overgrowth (SIBO) must be differentiated from other diseases that cause chronic diarrhea.

The following table outlines the major differential diagnoses of chronic diarrhea.[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]

Abbreviations: GI: Gastrointestinal, CBC: Complete blood count, WBC: White blood cell, RBC: Red blood cell, Plt: Platelet, Hgb: Hemoglobin, ESR: Erythrocyte sedimentation rate, CRP: C–reactive protein, IgE: Immunoglobulin E, IgA: Immunoglobulin A, ETEC: Escherichia coli enteritis, EPEC: Enteropathogenic Escherichia coli, EIEC: Enteroinvasive Escherichia coli, EHEC: Enterohemorrhagic Escherichia coli, EAEC: Enteroaggregative Escherichia coli, Nl: Normal, ASCA: Anti saccharomyces cerevisiae antibodies, ANCA: Anti–neutrophil cytoplasmic antibody, DNA: Deoxyribonucleic acid, CFTR: Cystic fibrosis transmembrane conductance regulator, SLC10A2: Solute carrier family 10 member 2, SeHCAT: Selenium homocholic acid taurine or tauroselcholic acid, IEL: Intraepithelial lymphocytes, MRCP: Magnetic resonance cholangiopancreatography, ANA: Antinuclear antibodies, AMA: Anti-mitochondrial antibody, LDH: Lactate dehydrogenase, CPK: Creatine phosphokinasePCR: Polymerase chain reaction, ELISA: Enzyme–linked immunosorbent assay, LT: Heat–labile enterotoxin, ST: Heat–stable enterotoxin, RT-PCR: Reverse–transcriptase polymerase chain reaction, CD4: Cluster of differentiation 4, HIV: Human immunodeficiency virus, RUQ: Right-upper quadrant, VIP: Vasoactive intestinal peptide, GI: Gastrointestinal, FAP: Familial adenomatous polyposis, HNPCC: Hereditary nonpolyposis colorectal cancer, MTP: Microsomal triglyceride transfer protein, Scl‑70: Anti–topoisomerase I, TSH: Thyroid-stimulating hormone, T4: Thyroxine, T3: Triiodothyronine, DTR: Deep tendon reflex, RNA: Ribonucleic acid

Cause Clinical manifestation Lab findings Extra intestinal findings Cause/Pathogenesis Gold standard diagnosis
Symptoms GI signs
Duration Diarrhea Fever Abdominal pain Weight loss
Stool exam CBC Other lab findings
Acute Chronic Watery Bloody Fatty WBC RBC Ova/Parasite Osmotic gap Other WBC Hgb Plt
Crohn's disease + + + + ± + + + + Nl
  • Abnormal immune response to self antigens
Ulcerative colitis + + + + ± + + + + Nl
  • Abnormal immune response to self antigens
Celiac disease + ± ± + + Nl Nl Nl
Cause Duration Diarrhea Fever Abdominal pain Weight loss GI signs Stool exam CBC Other lab findings Extra intestinal findings Cause/Pathogenesis Gold standard diagnosis
Acute Chronic Watery Bloody Fatty WBC RBC Ova/Parasite Osmotic gap Other WBC Hgb Plt
Cystic fibrosis + + ± + + Nl Nl Nl
Chronic pancreatitis + + + + + Nl Nl Nl Nl
Bile acid malabsorption + + + + Nl Nl Nl Nl
Microscopic colitis + + + + Nl Nl Nl
Cause Duration Diarrhea Fever Abdominal pain Weight loss GI signs Stool exam CBC Other lab findings Extra intestinal findings Cause/Pathogenesis Gold standard diagnosis
Acute Chronic Watery Bloody Fatty WBC RBC Ova/Parasite Osmotic gap Other WBC Hgb Plt
Infective colitis + + + + + + + + + Nl
Ischemic colitis + + + + + + + + + Nl
Lactose intolerance + + + + Nl Nl Nl
  • Lactose tolerance test
  • Genetic testing
  • Reduction of lactase enzyme activity or inability to produce persistent lactase
  • Congenital lactase deficiency
  • Secondary lactose malabsorption
Irritable bowel syndrome + ± ± ± Nl Nl Nl Nl Nl
  • Unknown
  • Diagnosis of exclusion
Cause Duration Diarrhea Fever Abdominal pain Weight loss GI signs Stool exam CBC Other lab findings Extra intestinal findings Cause/Pathogenesis Gold standard diagnosis
Acute Chronic Watery Bloody Fatty WBC RBC Ova/Parasite Osmotic gap Other WBC Hgb Plt
Whipple's disease + + + ± + + Nl ↓/↑
Tropical sprue + + + + + + + + Nl Nl Nl
  • Diagnosis of exclusion
Small bowel bacterial overgrowth + + + + + + Nl Nl Nl
  • Diagnosis of exclusion
Cause Duration Diarrhea Fever Abdominal pain Weight loss GI signs Stool exam CBC Other lab findings Extra intestinal findings Cause/Pathogenesis Gold standard diagnosis
Acute Chronic Watery Bloody Fatty WBC RBC Ova/Parasite Osmotic gap Other WBC Hgb Plt
Salmonellosis + + + + + + + + Nl Nl
Escherichia coli enteritis EPEC + + + + + + + + + Nl Nl Nl
EAEC + + + + + + + Nl
Aeromonas + + + + + + + + Nl Nl Nl
Cause Duration Diarrhea Fever Abdominal pain Weight loss GI signs Stool exam CBC Other lab findings Extra intestinal findings Cause/Pathogenesis Gold standard diagnosis
Acute Chronic Watery Bloody Fatty WBC RBC Ova/Parasite Osmotic gap Other WBC Hgb Plt
Mycobacterium avium complex + + + + + + + + Nl Nl
CMV colitis + + + ± + + + Nl
  • Viral antigen assay
Nl Nl
HIV + + + + + + Nl Nl
  • HIV virologic (viral load) test
  • Immunoassay 
Cause Duration Diarrhea Fever Abdominal pain Weight loss GI signs Stool exam CBC Other lab findings Extra intestinal findings Cause/Pathogenesis Gold standard diagnosis
Acute Chronic Watery Bloody Fatty WBC RBC Ova/Parasite Osmotic gap Other WBC Hgb Plt
Entamoeba histolytica + + + + + + + + + Nl Nl Nl
  • Antigen testing
  • Serology 
Giardia + + + + + + Nl Nl Nl Nl
  • Antigen detection assays
Cryptosporidium + + + + + Nl
  • Positive stool microscopy
Nl Nl Nl
  • Polymerase chain reaction
Microsporidia + + + + + + Nl
  • Positive stool microscopy
Nl Nl Nl
  • Decreased CD4 count
  • Antigen detection assays
Isospora + + + + + + + + + + Nl Nl Nl
  • Detecting oocysts in the feces
Cause Duration Diarrhea Fever Abdominal pain Weight loss GI signs Stool exam CBC Other lab findings Extra intestinal findings Cause/Pathogenesis Gold standard diagnosis
Acute Chronic Watery Bloody Fatty WBC RBC Ova/Parasite Osmotic gap Other WBC Hgb Plt
Carcinoid tumor + + + + + + Nl Nl Nl
VIPoma + + + + + + Nl Nl Nl
  • Primary secretory tumor
  • Blood VIP levels
  • Followed by imaging
Zollinger–Ellison syndrome + + + + + + Nl Nl
Somatostatinoma + + + + Nl Nl Nl
Cause Duration Diarrhea Fever Abdominal pain Weight loss GI signs Stool exam CBC Other lab findings Extra intestinal findings Cause/Pathogenesis Gold standard diagnosis
Acute Chronic Watery Bloody Fatty WBC RBC Ova/Parasite Osmotic gap Other WBC Hgb Plt
Lymphoma + + + + + + + Nl Nl Nl
  • Primary tumor of GI tract
Colorectal cancer + + + + + + + Nl Nl Nl
Medications + + + ± ± + + ↑/↓ Nl Nl
  • Elevated plasma level of drug
  • Clinical evaluation after discontinuation of the drugs
Factitious diarrhea + + + + + ↑/↓ Nl Nl Nl
  • Clinical evaluation after discontinuation of the drugs
Cause Duration Diarrhea Fever Abdominal pain Weight loss GI signs Stool exam CBC Other lab findings Extra intestinal findings Cause/Pathogenesis Gold standard diagnosis
Acute Chronic Watery Bloody Fatty WBC RBC Ova/Parasite Osmotic gap Other WBC Hgb Plt
Heavy metal ingestion + + + + Nl Nl Nl Nl
  • Elevated plasma heavy metal level
  • Plasma level of heavy metal
Organophosphate poisoning + + + + Nl Nl Nl Nl
  • Clinical diagnosis
Opium withdrawal + + + + Nl Nl Nl Nl
Cause Duration Diarrhea Fever Abdominal pain Weight loss GI signs Stool exam CBC Other lab findings Extra intestinal findings Cause/Pathogenesis Gold standard diagnosis
Acute Chronic Watery Bloody Fatty WBC RBC Ova/Parasite Osmotic gap Other WBC Hgb Plt
Short bowel syndrome + + + + + Nl Nl
Radiation enteritis + + + + + + + + + Nl Nl Nl
Dumping syndrome + + + + Nl Nl Nl Nl
Cause Duration Diarrhea Fever Abdominal pain Weight loss GI signs Stool exam CBC Other lab findings Extra intestinal findings Cause/Pathogenesis Gold standard diagnosis
Acute Chronic Watery Bloody Fatty WBC RBC Ova/Parasite Osmotic gap Other WBC Hgb Plt
Abetalipoproteinemia + + + + + Nl Nl Nl Nl
Hyperthyroidism + + ± + + Nl Nl Nl Nl
Diabetic neuropathy + + + + + Nl Nl Nl
Systemic sclerosis + + ± + + + + Nl Nl Nl
  • Clinical diagnosis
  • Followed by serologic tests


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