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Small Intestinal Bacterial Overgrowth


In its most simplistic form, the term SIBO describes a condition of excess bacteria in the small intestine. Although the phrase SIBO remains clinically relevant, it oversimplifies the rapidly evolving complexity of this disorder that has both intestinal and extra-intestinal manifestations. SIBO was first described in 1939 in patients with macrocytic anemia and intestinal strictures. Research studies on SIBO in the 1950s and 1960s focused on patients with prior intestinal surgery as the cause of their symptoms, especially those with an isolated loop of intestine. These initial studies defined SIBO by performing small intestine aspirates (primarily jejunal and duodenal) and culturing the fluid. SIBO was then defined as the presence of bacteria in the proximal small intestine of greater than 1 × 10 5 colony forming units (cfu)/mL. The impact of such overgrowth, or “contamination,” on a variety of intestinal functions and human nutrition was elegantly demonstrated in a series of classic studies performed during the 1950s through the 1970s. This solitary definition persisted for decades until changes in technology (e.g., breath testing) and new knowledge of disease states potentially associated with SIBO (e.g., IBS) forced investigators and clinicians to expand the definition of SIBO. Although controversial, advances in our knowledge of the intestinal microbiome, combined with an increased awareness of how its alterations influence health and promote disease, have led scientists and clinicians to challenge the current concept of SIBO. This chapter presents contemporary data on defining, diagnosing, and treating SIBO.

Definition

SIBO can be diagnosed as the presence of excess bacteria (either quantitative [>10 5 cfu/mL] or qualitative [excess bacteria of colonic origin] in the small intestine accompanied by intestinal or extra-intestinal symptoms thought to result from this excess.

Recognizing that a validated “gold standard” to quantitate excess small intestinal bacteria does not exist, and that diagnostic tests are not readily available to all clinicians, the definition of SIBO does not mandate that a specific test be used to make the diagnosis (e.g., culture or breath test; see “Diagnosis” section). The definition is also meant to convey that a spectrum of symptoms and disorders may develop because of SIBO. One end of this spectrum consists of what is considered “classic” SIBO, in which an overgrowth of bacteria is documented and symptoms of malabsorption, maldigestion, and steatorrhea are present. In this situation, the clinical presentation is related to the effects of the overabundance of organisms on host intestinal morphology or function ( Table 105.1 ), which, in turn, results in the clinical consequences typically associated with SIBO (e.g., steatorrhea, diarrhea, protein-losing enteropathy, and/or specific deficiency states). The other end of the spectrum reflects SIBO associated with symptoms or clinical entities in the absence of evidence of maldigestion/malabsorption (e.g., SIBO in association with IBS). In this situation, the pathophysiologic link with SIBO is less clearly defined. This scenario, essentially an “expanded” version of SIBO, has proved more problematic because much of the evidence used to support an association between SIBO and a given entity has been based on the performance characteristics of the test used to define it and, more specifically, on the ability of that test to distinguish health from disease. However, as discussed in the Diagnosis section, a consensus regarding standardization of tests to accurately diagnose SIBO is lacking. Thus, in some situations, it may not be clear whether SIBO is a cause, a consequence, or an epiphenomenon in relation to the supposedly associated disorder.

TABLE 105.1
Pathophysiology of Symptoms and Clinical Consequences in Small Intestinal Bacterial Overgrowth
Pathophysiologic Process Intestinal or Luminal Results Clinical Consequences
Mucosal injury induced by bacteria and/or their toxins or metabolic products Loss of brush-border enzymes Carbohydrate maldigestion and malabsorption
Injury to epithelial barrier leading to enhanced intestinal permeability Protein-losing enteropathy; bacterial translocation and portal and systemic endotoxemia
Inflammatory response generating inflammatory cytokines Liver injury and inflammation, systemic inflammatory responses
Luminal competition with the host for nutrients Consumption of dietary protein Hypoproteinemia, edema
Consumption of vitamin B 12 ; production of cobamides B 12 deficiency, megaloblastic anemia, neurologic symptoms
Consumption of thiamine Thiamine deficiency
Consumption of nicotinamide Nicotinamide deficiency
Bacterial metabolism Fermentation of unabsorbed carbohydrates Bloating, distension, flatulence; auto-brewery syndrome
Diarrhea due to the effects of deconjugated bile acids in the colon; depletion of the bile acid pool leading to fat and fat-soluble vitamin malabsorption
Deconjugation of primary bile acids
Synthesis of vitamin K Interference with dosing of vitamin K antagonists (e.g., warfarin)
Synthesis of folate High serum folate levels
Synthesis of d -lactic acid d -lactic acidosis
Synthesis of alcohol Liver injury, auto-brewery syndrome
Synthesis of acetaldehyde Liver injury

Pathogenesis

The human GI microbiota is a complex ecosystem comprising approximately 500 distinct bacterial species. The vast majority of these bacteria are found in the colon, which contains approximately the same number of living cells as the rest of the entire body. The bacterial content of the small intestine is drastically lower than that of the colon for 3 major reasons: (1) gastric acid prevents bacterial overgrowth in the stomach and proximal small intestine; (2) normal fasting intestinal motor activity (i.e., migrating motor complex) prevents accumulation of bacteria within the small intestine; (3) the ileocecal valve limits reflux of colonic bacteria into the distal small intestine. Because the small intestine is the site of digestion and absorption of food, maintaining low numbers of bacteria in the small intestine is beneficial to the host to prevent unwanted competition for nutrients, minimize abnormal entry of bacteria across the more permeable epithelium of the small intestine, and reduce gas production from bacterial fermentation of food.

SIBO can develop for a number of reasons ( Box 105.1 ) and can produce marked changes in intestinal morphology and physiology, which were elegantly demonstrated in a series of classic clinical and laboratory-based studies performed during the latter half of the last century (see Table 105.1 ).

BOX 105.1
Diseases and Disorders Linked to SIBO Based on Pathophysiology

Intestinal Dysmotility

  • Acromegaly

  • Amyloidosis and other infiltrative disorders of the small intestine

  • Diabetic autonomic neuropathy

  • Gastroparesis

  • Hypothyroidism

  • Idiopathic intestinal pseudo-obstruction (e.g., opioids, anticholinergic agents, some antipsychotics; high-dose tricyclic antidepressants)

  • Medications that suppress intestinal motility (e.g., opioids, anticholinergic agents, some antipsychotics; high-dose tricyclic antidepressants)

  • Myotonic muscular dystrophy

  • Systemic sclerosis/scleroderma

Altered Anatomy

  • Blind loops

    • Gastrocolic or jejunocolic fistula

    • Ileocecal valve resection

    • Small intestinal diverticulosis

    • Strictures (Crohn disease, radiation, surgery)

    • Surgical alterations in anatomy (e.g., Billroth II gastrectomy, end-to-side anastomosis, Roux-en-Y gastric bypass)

  • Obstruction

Hypochlorhydria

  • Long-term acid suppression (possibly only at high dose)

  • Postsurgical

Immune Deficiency

  • Acquired immune deficiency (e.g., AIDS, severe malnutrition)

  • Inherited immune deficiencies

Multifactorial Causes

  • Advanced age

  • Celiac disease

  • Chronic pancreatitis

  • Crohn disease

  • Cystic fibrosis

  • End-stage kidney disease

  • Intestinal failure

  • Liver disease

  • Radiation enteropathy

  • Tropical sprue

Unclear or Undefined Relationship to SIBO

  • IBS

  • Interstitial cystitis

  • Parkinson disease

  • Psychiatric disorders (e.g., anxiety, depression)

  • Restless legs syndrome

  • Rosacea

  • Severe obesity

Mucosal Injury

In some patients with SIBO, especially those with evidence of malabsorption, mucosal injury (often microscopic) contributes to symptoms due to the loss of brush border enzymes (e.g., lactase, maltase, sucrase-isomaltase, trehelase, peptidases). The loss of brush border disaccharidases results in the presentation of more unabsorbed carbohydrates to intestinal bacteria for fermentation and may contribute to lactose intolerance. Damage to the epithelial barrier will enhance permeability and, in the most severe cases, may lead to protein-losing enteropathy (see Chapter 31 ). Enterotoxins elaborated by some species may further exacerbate mucosal injury, although such injury in SIBO is usually not grossly apparent and histologically appears as only minor nonspecific changes in villus form with an inflammatory response; generation of inflammatory cytokines, such as TNF-α, may contribute to hepatic and systemic complications.

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