Pathophysiology of SIBO
SIBO develops when protective mechanisms that normally prevent bacterial colonization of the small intestine fail, allowing colonic bacteria to proliferate in stagnant loops of bowel, leading to malabsorption through bile salt deconjugation and pancreatic enzyme degradation 1.
Core Protective Mechanisms That Fail in SIBO
The small intestine normally maintains bacterial concentrations below 10⁴ colony forming units (cfu)/mL through several endogenous defense mechanisms 1, 2:
- Gastric acid secretion - Creates hostile environment for bacteria
- Intestinal motility and the Migrating Myoelectric Complex (MMC) - Clears debris and prevents stasis
- Intact ileocecal valve - Prevents retrograde bacterial migration from colon
- Intestinal immunoglobulin secretion - Provides immune surveillance
- Bacteriostatic properties of pancreatic and biliary secretions - Directly inhibit bacterial growth
When one or more of these mechanisms becomes impaired, the aetiology of SIBO is usually complex and multifactorial 1.
The Pathophysiological Cascade
1. Impaired MMC and Gut Stasis
When the MMC is disrupted, the small bowel cannot clear debris, predisposing to gut stasis and bacterial overgrowth 1. This occurs through:
- Loss of coordinated gut contractions
- Failure of forward propulsion causing constipation
- Dilated gut with reduced propulsion
- Accumulation of chyme triggering severe painful non-propulsive contractions (explaining postprandial abdominal pain)
2. Bacterial Proliferation in Stagnant Loops
The combination of dilated gut with reduced propulsion and ineffective MMC allows anaerobic bacteria to proliferate in stagnant loops of bowel 1. The normal small intestinal bacterial concentration of <10⁴ cfu/mL increases dramatically, with >10⁶ cfu/mL conventionally regarded as diagnostic 2.
3. Metabolic Consequences of Bacterial Overgrowth
The proliferating bacteria cause malabsorption through direct metabolic effects 1:
Bile salt deconjugation:
- Bacteria deconjugate bile salts
- Less effective secondary bile acids (e.g., lithocholic acid) are produced
- Results in steatorrhea and malnutrition
Pancreatic enzyme degradation:
- Bacterial enzymes degrade pancreatic lipase, amylase, and trypsin
- Further impairs digestion of fats, carbohydrates, and proteins
Fat-soluble vitamin malabsorption:
- Vitamins A and E primarily affected (less so D, rarely K)
- Causes night blindness, poor color vision, dry flaky skin, and ataxia
Vitamin B12 malabsorption:
- Bacteria consume B12 before host absorption
- Paradoxically, folic acid and vitamin K may be manufactured by bacteria, giving rise to high serum levels
4. Toxic Bacterial Metabolites
Bacteria can produce pathological metabolites 1:
- D-lactic acid (normally L-isomer) → D-lactic acidosis with high anion gap
- Ammonia → elevated blood ammonia levels
- Excessive fermentation → gas production, bloating, and distension
5. Mucosal Damage
SIBO leads to a malabsorption syndrome with occasionally protein-losing enteropathy 1. Subtotal villous atrophy may be found on histology, demonstrating direct mucosal injury from bacterial overgrowth.
Clinical Context and Predisposing Factors
SIBO occurs most commonly in patients with 1, 2, 3:
- Anatomical abnormalities: Bowel obstruction, diverticula, surgical alterations, blind loops
- Motility disorders: Enteric neuropathies, chronic intestinal pseudo-obstruction, diabetes
- Achlorhydria: Proton pump inhibitor use, atrophic gastritis, advanced age
- Immunosuppression: Reduced intestinal immunoglobulin secretion
- Pancreatic insufficiency: Loss of bacteriostatic pancreatic secretions 4
Important Caveats
The pathophysiological framework described above applies to "classical" SIBO in the context of maldigestion/malabsorption 5, 6. The extension of SIBO diagnosis to explain symptoms in irritable bowel syndrome and other functional disorders lacks the same pathophysiological plausibility 5, 6. Breath tests used in these contexts are subject to misinterpretation, and the clinical relevance of bacterial overgrowth detected in apparently healthy individuals remains unclear 2, 6.
The undernutrition resulting from SIBO creates a vicious cycle: malabsorption leads to mucosal atrophy, reduced gastric acid and pancreatic enzyme secretion, and more bacterial colonization of the upper gut 1.