Small intestinal bacterial overgrowth syndrome

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Mazia Fatima, MBBS [2]

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

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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, 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, 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, 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 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.
• 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. 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.

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 phosphokinase, PCR: 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		–	+	+	+	+	±	+	+	Abdominal tenderness Oral mucosal lesions	+	+	–	Nl	–	↑	↓	↑	Anti saccharomyces cerevisiae antibodies (ASCA) Vitamin B12 deficiency Elevated ESR Elevated CRP	Uveitis Arthritis Erythema nodosum Pyoderma gangrenosum Amyloidosis Venous and arterial thromboembolism Renal stones Bronchiectasis	Abnormal immune response to self antigens	Colonoscopy with biopsy
Ulcerative colitis		–	+	+	+	+	±	+	+	Abdominal tenderness Blood on rectal examination	+	+	–	Nl	–	↑	↓	↑	Anti–neutrophil cytoplasmic antibody (P–ANCA) Hypoalbuminemia Hypokalemia Hypomagnesemia Elevated ESR Elevated CRP	Skin rash Iritis Uveitis Seronegative arthritis Clubbing Erythema nodosum	Abnormal immune response to self antigens	Colonoscopy with biopsy
Celiac disease		–	+	±	–	±	–	+	+	Abdominal distention Increased bowel sounds Oral mucosal lesions Hepatosplenomegaly Ascites	–	–	–	Nl	Fat droplets on sudan stain	Nl	↓	Nl	IgA endomysial antibody Anti–tissue transglutaminase antibody Anti–gliadin antibody Fat soluble vitamins deficiency	Malabsorption Dementia Dermatitis herpetiformis	HLA–DQ2 HLA–DQ8 Innate responses to wheat proteins	IgA endomysial antibody Anti–tissue transglutaminase antibody
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		–	+	–	–	+	±	+	+	Abdominal distention Hepatosplenomegaly Rectal prolapse	–	–	–	Nl	Fat droplets on sudan stain	Nl	↓	Nl	Positive DNA analysis for cystic fibrosis transmembrane conductance regulator (CFTR) Nasal transepithelial potential difference Fat soluble vitamins deficiency	Malabsorption Recurrent respiratory tract infection Bronchiectasis Diabetes mellitus Scoliosis Infertility	Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein	Positive genetic testing Elevated sweat chloride ≥60 mmol/L
Chronic pancreatitis		–	+	+	–	+	–	+	+	Abdominal tenderness	–	–	–	Nl	Fat droplets on sudan stain Positive fecal elastase measurement	Nl	Nl	Nl	Slightly elevated amylase and lipase Abnormal pancreatic function test Secretin stimulation test	Malabsorption Diabetes mellitus Pancreatic pseudocyst	Toxins Recurrent acute pancreatitis Genetic predesposition Autoimmune	Magnetic resonance cholangiopancreatography (MRCP)
Bile acid malabsorption		–	+	+	–	+	–	–	+		–	–	–	Nl	Fat droplets on sudan stain	Nl	Nl	Nl	Reduced cholesterol level	Malabsorption Hypotension Tachycardia	Genetic defects in SLC10A2	SeHCAT test
Microscopic colitis		–	+	+	–	–	–	+	+	Abdominal tenderness Fecal incontinence	–	–	–	Nl	–	Nl	↓	Nl	Hypokalemia Elevated CRP Positive autoantibodies include: RF ANA AMA ANCA	Arthritis Uveitis Idiopathic thrombocytopenic purpura Pleuro pericarditis Hypothyroidism Psoriasis	Mucosal immune responses to luminal factors in a genetically predisposed individual Drug–induced	Colonoscopy with mucosal biopsy with mononuclear infiltrates: Collagenous colitis is characterized by a colonic subepithelial collagen band >10 micrometers in diameter Lymphocytic colitis is characterized by ≥20 intraepithelial lymphocytes (IEL) per 100 surface epithelial cells
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		–	+	+	+	–	+	+	+	Rebound abdominal tenderness	+	+	+	Nl	Positive stool culture Positive fecal calprotectin Positive fecal lactoferrin	↑	↓	↑	Elevated CRP Elevated ESR	Arthritis Uveitis	Salmonella Shigella Campylobacter E. coli 0157:H7 Clostridium difficile Entamoeba histolytica Adenovirus Cytomegalovirus Herpes simplex virus	Stool culture Blood culture
Ischemic colitis		+	+	+	+	–	+	+	+	Hyperactive then absent bowel sounds Abdominal tenderness	+	+	–	Nl	–	↑	↓	↑	Elevated CRP Elevated ESR Elevated serum lactate Elevated lactate dehydrogenase (LDH) Elevated creatine phosphokinase (CPK) Elevated amylase Hypoalbuminemia	IgA vasculitis	Hypercoagulability Nonocclusive colonic ischemia Embolic and thrombotic arterial occlusion Mesenteric vein thrombosis	Abdominal CT scan
Lactose intolerance		+	+	+	–	–	–	+	–	Abdominal tenderness Abdominal distention	–	–	–	↑	–	Nl	Nl	Nl	Lactose tolerance test Genetic testing	Headache Vertigo Memory impairment Lethargy	Reduction of lactase enzyme activity or inability to produce persistent lactase Congenital lactase deficiency Secondary lactose malabsorption	Small bowel biopsy Lactose breath hydrogen test
Irritable bowel syndrome		–	+	±	–	±	–	±	–	Abdominal tenderness Abdominal distention Normal bowel sounds	–	–	–	Nl	–	Nl	Nl	Nl	Nl	Anxiety Palpitation	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		–	+	+	–	+	±	+	+	Hepatosplenomegaly Ascites	–	–	–	Nl	Positive fecal fat	↓	↓	↓/↑	Hypoalbuminemia Fat soluble vitamins deficiency	Malabsorption Abnormal extraocular movement Lymphadenopathy Hyperpigmentation Uveitis Endocarditis Encephalitis Dementia Pleural effusion	Tropheryma whipplei	Small intestine biopsy for Tropheryma whipplei testing PCR testing
Tropical sprue		+	+	+	–	+	+	+	+	Angular stomatitis Oral mucosal lesion	+	–	–	Nl	Positive stool culture	Nl	↓	Nl	Fat soluble vitamins deficiency Vitamin B12 deficiency Folate deficiency Hypokalemia	Myalgia Neuropathy Edema	Escherichia coli Klebsiella pneumoniae Enterobacter cloacae	Diagnosis of exclusion
Small bowel bacterial overgrowth		–	+	+	–	+	–	+	+	Abdominal distention	+	–	–	Nl	Positive stool culture Positive fecal fat	Nl	↓	Nl	Hypoalbuminemia Abnormal hydrogen breath test Lactic acidosis	Malabsorption Rosacea	Excess bacteria in the small intestine Alterations in intestinal anatomy or GI motility	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		+	+	+	+	–	+	+	–	Abdominal distention Diffuse abdominal tenderness Hepatosplenomegaly	+	+	–	Nl	Positive stool culture Positive serologic testing	↑	Nl	↑	Hypokalemia Hypernatremia Hyponatremia Hypercalciuria Hypocitraturia	Post–infectious arthritis Obtundation Bacteremia Pericarditis Pyelonephritis Brain abscess	Salmonella	Stool culture
Escherichia coli enteritis	EPEC	+	+	+	+	–	+	+	+	Diffuse abdominal tenderness	+	+	–	Nl	Positive stool culture	↑	Nl	Nl	–	–	Enteropathogenic E. coli	DNA probe or polymerase chain reaction (PCR) of the EPEC adherence factor Stool culture
	EAEC	+	+	+	+	–	–	+	–	Diffuse abdominal tenderness	+	+	–	Nl	Positive stool culture	↑	↓	↓	–	Chronic infection in immunocompromised patients	Enteroaggregative E. coli	Stool culture
Aeromonas		+	+	+	+	–	+	+	–	Abdominal distention Hyperactive bowel sounds Diffuse abdominal tenderness	+	+	–	Nl	Positive stool culture	↑	Nl	Nl	–	Wound infection Bacteremia Hemolytic uremic syndrome Meningitis Ocular infection Pneumonia Urinary tract infection Osteomyelitis Peritonitis Acute cholecystitis Opportunistic infections in immunocompromised patients	Aeromonas virulence factors including endotoxins, hemolysins, enterotoxins, and adherence factors	Blood culture Wound culture
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		+	+	+	+	–	+	+	–	Abdominal distention Hepatosplenomegaly	+	+	–	Nl	–	↓	↓	Nl	Elevated liver enzymes	Opportunistic infection in immunocompromised patients Pulmonary infection Adenopathy Night sweats	Mycobacterium avium complex	Blood culture
CMV colitis		+	+	–	+	–	±	+	–	Diffuse abdominal tenderness	+	+	–	Nl	Viral antigen assay	↓	Nl	Nl	Decreased CD4 level Abnormal liver function test	Encephalitis Guillain–Barré syndrome Pneumonia Retinitis Pericarditis and myocarditis Atherosclerosis Venous thrombosis	Cytomegalovirus	Quantitative PCR tests
HIV		–	+	+	–	–	+	+	+	Abdominal distention Diffuse abdominal tenderness	+	–	–	Nl	–	↓	↓	Nl	Decreased CD4 level Electrolyte imbalance	Lymphadenopathy Disseminated infection	HIV	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		+	+	+	+	–	+	+	–	Abdominal distention Diffuse abdominal tenderness	+	+	+	Nl	–	↑	Nl	Nl	–	Liver abscess Pleuropulmonary infection Cardiac infection Brain abscess Cutaneous infection	Entamoeba histolytica	Antigen testing Serology
Giardia		–	+	+	–	+	–	+	+	Abdominal distention Diffuse abdominal tenderness	–	–	+	Nl	–	Nl	Nl	Nl	–	Malabsorption Urticaria Depression	Giardia lamblia	Antigen detection assays
Cryptosporidium		–	+	+	–	–	–	+	+	Abdominal distention Diffuse abdominal tenderness	–	–	+	Nl	Positive stool microscopy	Nl	Nl	Nl	Elevated alkaline phosphatase	Chronic, life–threatening illness in immunocompromised patients	Cryptosporidium	Polymerase chain reaction
Microsporidia		+	+	+	–	–	+	+	–	Abdominal distention Diffuse abdominal tenderness	–	–	+	Nl	Positive stool microscopy	Nl	Nl	Nl	Decreased CD4 count	Malabsorption Keratitis Seizure Myositis	Microsporidia	Antigen detection assays
Isospora		+	+	+	–	+	+	+	+	Abdominal distention Diffuse abdominal tenderness	+	+	+	Nl	Positive stool microscopy Positive fecal fat	↑	Nl	Nl	Elevated eosinophils Hypokalemia Increased creatinine	Chronic illness in immunocompromised patients	Isospora	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		–	+	+	+	–	–	+	+	Abdominal distention	–	+	–	↓	–	Nl	Nl	Nl	Elevated urinary 5–hydroxyindoleacetic acid (5–HIAA) level High chromogranin A	Facial flushing Jaundice Edema Valvular heart disease Right–sided heart failure	Well–differentiated neuroendocrine tumor	Blood chromogranin A level
VIPoma		+	+	+	–	+	–	+	+	Abdominal distention Abdominal RUQ tenderness Nausea Vomiting	–	–	–	↓	–	Nl	Nl	Nl	Elevated VIP level Hypokalemia Hypochlorhydria or achlorhydria Low osmotic gap (<50 mOsm/kg)	Rash Facial flushing Dehydration Lethargy Muscle weakness	Primary secretory tumor	Blood VIP levels Followed by imaging
Zollinger–Ellison syndrome		–	+	+	+	+	–	+	+	Epigastric tenderness	–	–	–	↓	–	Nl	↓	Nl	Positive secretin stimulation test Elevated serum chromogranin A	Jaundice	Gastrin producing tumor mainly in duodenum	Secretin stimulation test
Somatostatinoma		–	+	+	–	–	–	+	+	Epigastric tenderness	–	–	–	↓	–	Nl	Nl	Nl	Elevated fasting plasma somatostatin	Diabetes mellitus Cholelithiasis Jaundice	Neuroendocrine tumors of D–cell origin	Plasma somatostatin level Followed by imaging
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		–	+	+	+	–	+	+	+	Diffuse abdominal tenderness Hepatosplenomegaly	–	+	–	Nl	–	Nl	↓	Nl	Paraproteinemia	Malabsorption Lactose intolerance Ascites	Primary tumor of GI tract	Colonoscopy with biopsy
Colorectal cancer		–	+	+	+	+	–	+	+	Diffuse abdominal tenderness	–	+	–	Nl	–	Nl	↓	Nl	Positive carcinoembryonic antigen	Metastasis	FAP gene HNPCC gene	Colonoscopy and biopsy
Medications ACE inhibitors Digoxin Cephalosporins Statins Thiazide diuretics Triptans Lactulose Anti retroviral agents Chemotherapeutic agents Antifungals Magnesium		+	+	+	–	±	±	+	+	Abdominal distention Dehydration	–	–	–	↑/↓	–	↑	Nl	Nl	Elevated plasma level of drug	–	Inflammation Pseudomembranous colitis	Clinical evaluation after discontinuation of the drugs
Factitious diarrhea		+	+	+	–	–	–	+	+	Abdominal distention	–	–	–	↑/↓	–	Nl	Nl	Nl	Hypokalemia Metabolic alkalosis Hypermagnesemia	Malabsorption Lethargy Generalized weakness Acute renal failure	Medications	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		–	+	+	–	–	–	+	+	Abdominal distention	–	–	–	Nl	–	Nl	Nl	Nl	Elevated plasma heavy metal level	Headache Numbness Alopecia Vertigo	Heavy metal ingestion	Plasma level of heavy metal
Organophosphate poisoning		+	+	+	–	–	–	+	–	Salivation Vomiting	–	–	–	Nl	–	Nl	Nl	Nl	Reduced RBC acetylcholinesterase Plasma cholinesterase activity	Autonomic dysfunction Motor deficit Sensory deficit Bronchospasm Urination Miosis Bradycardia Lacrimation Sweating Cardiac arrhythmias Acute renal injury	Neurotoxins bind to acetylcholinesterase (AChE)	Clinical diagnosis
Opium withdrawal		+	+	+	–	–	–	+	–	Hyperactive bowel sounds	–	–	–	Nl	–	Nl	Nl	Nl	Azotemia Hypokalemia Metabolic alkalosis	Dysphoria Restlessness Sweating Rhinorrhea Lacrimation Myalgia Arthralgia	Opium withdrawal	Clinical diagnosis following opium withdrawal
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		+	+	+	–	+	–	–	+	Abdominal distention Abdominal tenderness	–	–	–	Nl	Positive fecal fat	Nl	↓	↑	Hypoalbuminemia High level of acute phase reactant Abnormal liver function tests	Prior intestinal surgery Malabsorption Crohn's disease Malignancy Peripheral edema Muscle atrophy	Surgical bowel resection	Clinical diagnosis following bowel resection
Radiation enteritis		+	+	+	+	+	–	+	+	Abdominal tenderness	+	+	–	Nl	Positive fecal fat	Nl	↓	Nl	Vitamin B12 deficiency Hypoalbuminemia	Prior history of malignancy and radiation therapy Malabsorption Telangiectasias	Radiation	Segmental bowel inflammation on endoscopy or colonoscopy
Dumping syndrome		–	+	+	–	+	–	–	+	Hyperactive bowel sound	–	–	–	Nl	–	Nl	Nl	Nl	Hypoglycemia Hydrogen breath test	Malnutrition Fat soluble vitamin deficiency	Postgastrectomy	Clinical diagnosis following gastrectomy
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		–	+	+	–	+	–	+	+	Abdominal distension	–	–	–	Nl	–	Nl	Nl	Nl	Low triglyceride Low total cholesterol levels Acanthocytes Low vitamin E levels	Ataxia Visual field defect Dysarthria	Autosomal recessive disorder caused by mutations encoding the microsomal triglyceride transfer protein (MTP)	Clinical findings and low triglyceride and cholesterol level
Hyperthyroidism		–	+	+	–	–	±	+	+	–	–	–	–	Nl	Positive fecal fat	Nl	Nl	Nl	Elevated T4 Elevated T3 Decreased TSH High serum alkaline phosphatase	Lump in the neck Lid lag Malabsorption Sweating Hyperpigmentation Proptosis Tremor Increased DTR	Graves' disease Hashimoto's thyroiditis Toxic adenoma	TSH
Diabetic neuropathy		–	+	+	–	+	–	+	+	Fecal incontinence	–	–	–	Nl	Positive fecal fat	Nl	↓	Nl	Hyperglycemia Azotemia Hypokalemia	Malabsorption	Unclear Disordered motility Increased intestinal secretion Small intestinal bacterial overgrowth	Clinical diagnosis in a patient with long lasting diabetes mellitus
Systemic sclerosis		–	+	+	±	+	–	+	+	Epigastric tenderness Fecal incontinence	–	+	–	Nl	Positive fecal fat	Nl	↓	Nl	Anti–topoisomerase I (Scl‑70) antibodies Antinuclear antibodies (ANA) Anti–centromere antibodies Anti–RNA polymerase III antibody	Malabsorption Skin changes Raynaud phenomenon Pulmonary hypertension Arthritis Telangiectasia Chronic renal failure	Autoimmune reaction	Clinical diagnosis Followed by serologic tests

Epidemiology and Demographics

• The prevalence of SIBO is unknown.

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

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/ 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

• 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
• Bacterial concentration of >103 units/mL in a jejunal aspirate culture

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 is diagnostic 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

Imaging Findings

• In CT abdomen/MRI may demonstrate associated strictures, malrotation, fistulae.

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.

Treatment

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).
  • Preferred regimen: Rifaximin 550 mg PO 8h 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.

External links

• IBS and small intestinal bacterial overgrowth (SIBO)

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