Understand the Causes

The science behind the symptoms of IBS-D is complex.1,2

A Multifactorial Disorder of Uncertain Etiology

The etiology of IBS remains unknown, although it is thought to be a multifactorial disease with different causative factors appearing in different combinations in each patient.3-5 The uncertainty of the underlying cause limits current treatment to an approach based on symptoms alone.1,2,5,6

The key causative factors potentially implicated in IBS include:
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Gut Microbiome Alterations

Recent research suggests that a healthy gut microbiome, characterized by high levels of bacterial diversity and temporal stability,33-36 plays an integral role in vital metabolic and signaling functions.33,37 In addition to digestion and absorption of nutrients, primary functions of a balanced microbiota include the production of vitamins and amino acids as well as certain neurotransmitters (eg, serotonin), and protection against pathogens through regulation of the intestinal immune system response.26,33,37

Although the exact etiology and pathogenesis of IBS-D is not well understood,3,33,38 data from multiple studies have shown reduced diversity and increased temporal instability of gut microbiota in patients with IBS-D compared with healthy controls.35,36,39-41 This imbalance in the composition of microbiota, or dysbiosis, is thought to contribute to the development of symptoms associated with IBS-D, including abdominal pain, bloating, and diarrhea.26,37-39

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While more research is needed, there is now general acceptance of the potential role gut microbiota play in the pathogenesis of IBS-D.26,36,42,43 More than 70% (80 of 109) of IBS patients in one study demonstrated alterations in the composition of gut microbiota (dysbiosis).44 An imbalance in the composition of microbiota is thought to contribute to the development of symptoms associated with IBS-D in some patients, including abdominal pain, bloating, and diarrhea.26,37-39

Potential Involvement of Altered Gut Microbiota in IBS-D Symptoms

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Gut Microbiome Alterations… May Lead to… Symptoms of IBS-D
Altered fermentation of poorly absorbable carbohydrates26,36-38,45 Production of excessive amounts of intestinal gases26,37,38,45
  • Abdominal pain26,38,45
  • Bloating26,38,45

Increased production of short-chain fatty acids (due to altered fermentation), resulting in release of 5-HT (serotonin) from the intestinal mucosa, acidification of the colon, and deconjugation of bile acid26,37-39,42,45,46

  • Increased colonic contractions26
  • Accelerated intestinal transit26,38,39
  • Increased gut motility26,38,39
  • Changes in water and electrolyte transport45,46
  • Diarrhea26,45-47

Activation of the intestinal immune system response and inflammation11,26,37,43,46-48

Impaired epithelial barrier function and increased intestinal permeability, resulting in release of neurotransmitters and inflammatory mediators that leads to3,11,26,37,39,40,46-48:

  • Visceral hypersensitivity
  • Smooth muscle contraction
  • Abnormal intestinal and abdominal reflex response
  • Disturbed intestinal transit
  • Abdominal pain11,47,48
  • Bloating11,36
  • Diarrhea11,47,48
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Back to Causative Factors

Genetic and Psychosocial Factors

People with a family history of IBS have a 2- to 3-fold increased risk for IBS.7,8 Genes that may be linked to IBS include those associated with the immune system and inflammatory response; the intestinal barrier and other GI functions; certain neurotransmitters (eg, serotonin, norepinephrine); and psychiatric disease.1,8,9

Psychosocial factors, including stress and early-life experiences with severe trauma—including childhood abuse—have been linked to the development of IBS.1,12,13 However, the relationship of psychosocial factors and IBS is not definitive.1

Psychiatric comorbidities associated with IBS were once thought to cause GI symptoms; however, there is now evidence that in many patients, GI symptoms can arise first and mood disorders occur later.13,14

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Genetics

In a survey of twins about the presence of GI disease, it was found that both identical twins had a greater likelihood to suffer from IBS than did fraternal twins, supporting a potential genetic contribution to the etiology of IBS.10

Prior Anxiety

Although prior anxiety can increase the risk of developing IBS, it is also true that severe GI symptoms can induce psychological distress. This association may reflect the bidirectional communication between emotional and cognitive brain centers and peripheral intestinal functions. Results of animal studies have shown that the gut microbiota may influence these interactions.14

Psychological Stress

Preclinical and clinical data have shown that psychological stress can cause physiologic change, including changes in the composition and function of gut microbiota.12,14-16 Stress has been associated with changes in bacteria in the Enterobacteriaceae family, Lactobacilli spp., Escherichia coli, and Pseudomonas spp.16,17 These bacteria have all been implicated in the development of IBS in patients.18-21

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Gut-Brain Axis Alterations

The bidirectional communication between the enteric nervous system (ENS) and the central nervous system (CNS) is called the gut-brain axis. Alterations in the gut-brain axis cause changes in nervous system responses and may lead to GI disorders, including IBS-D, which has been associated with psychiatric comorbidities.1,22,23

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The microbiome-gut-brain axis includes the ENS, CNS, autonomic nervous system, and hypothalamic-pituitary-adrenal (HPA) axis, as well as the gut microbiome.22,24,25 Signals sent back and forth along brain and spinal cord pathways help regulate food intake, digestion, gut sensations, and control of bowel movements.22 However, signals from the CNS that occur in response to stress or psychological disturbances can alter normal gut function, which could contribute to the visceral hypersensitivity and dysmotility in IBS-D.26

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Visceral Hypersensitivity

Pain is a prominent pathophysiologic feature of IBS.7 Visceral hypersensitivity is characterized by reduced pain threshold, or exaggerated response to painful stimuli.18,27 However, in the case of IBS-D, there is no apparent tissue injury or structural damage to warrant the increased sensitivity.28

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Pain associated with IBS has been attributed to alterations in the gut-brain axis, which cause normal sensory signals to be perceived as pain.28 It has also been linked to alterations in the composition of the gut microbiota.26,27 Animal studies have shown that contact with the microbiota is necessary for development of pain sensitivity, and that transfer of fecal microbiota from patients with IBS to germ-free rats resulted in a transfer of associated visceral hypersensitivity.27,29,30

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Increased Mucosal Permeability

Increased mucosal permeability in IBS-D was associated with activation of the intestinal immune system and inflammation.5,31,32 Factors that may increase mucosal permeability include stress, dietary intolerance, and prior infection.1,5,11

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When tight junctions in the GI tract are weakened, increased intestinal permeability initiates localized inflammation and the release of inflammatory mediators that alter neuromuscular function within the GI tract. This may lead to symptoms of abdominal pain and diarrhea.11

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How to Help Your Patients

IBS-D can greatly impact patients’ lives. Find out what you can do to help your patients.

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Treatment Options

Now that you understand the multifactorial nature of IBS-D pathogenesis, click below to learn about one possible treatment option.

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References +

 

References

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