Pathophysiology

IBS is a complex multifactorial disorder1-4

IBS is a complex multifactorial disorder

The precise molecular pathophysiology of IBS is not yet fully understood1-4

Multiple factors are implicated in the pathophysiology of IBS, including genetic predisposition, environmental and psychosocial factors, diet, gut microbiota, gut mucosal immune activation, and alterations in motility and fluid secretion1-4

Genetics

Studies of familial aggregation and twin studies suggest that genetics may play a role in IBS5,6

Function
Serotonin signaling pathways
Immune activation
Bile acid synthesis
Neuropeptide activity
Intestinal motility and visceral pain
General cell processes
Genes
HTR3E,9 SERT10
TNFSF15,11-14 TLR915,16
KLB17
NPSR118,19
SCN5A20
CDC42,13 KDELR221

Diet

Certain foods are known to trigger or exacerbate IBS symptoms, such as abdominal pain, bloating, and changes in bowel habits, in some patients22

Many patients with IBS may have some form of food intolerance (i.e. a physiological response to a food allergen not associated with an immune response)22

A very low proportion of patients with IBS have a food allergy (1-3%)23

See our symptom triggers page for more information on the role of food in IBS

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Environmental/psychosocial factors

The brain and the gut are closely linked in a bidirectional manner via the vagus nerve, as well as via other neural, hormonal, and immune mediators.24 This brain–gut axis plays a central role in IBS25

Studies have shown that psychosocial factors, such as a history of sexual or physical abuse, or other traumatic events in early life, are risk factors for IBS and can affect its onset and severity26,27

Stress is a key factor in the onset or exacerbation of symptoms for many people with IBS. Stress can affect both sides of the brain–gut axis, leading to2,24-28:

  • Increased sensitivity of intestinal nerves
  • Modification of central pain circuitry
  • Inflammation
  • Altered gut microbiota

Many people with IBS have comorbid psychiatric issues, such as anxiety or depression, underscoring the brain–gut connection with IBS, though whether these are causes or consequences of digestive problems is often unclear29

Environmental/psychosocial factors

Gut microbiota dysbiosis

In recent years, the role of the gut microbiota in both normal physiology and pathophysiology has been increasingly recognized, including in IBS25

The role of gut microbiota in metabolism, immune function, GI motility, and stress responses has led to recognition of the brain–gut–microbiota axis, and all three components of this axis are thought to intersect in IBS pathophysiology25,30,31

Diet, stress, and antibiotic use can all affect the gut microbiota composition. In patients with IBS, the dysbiosis of the gut microbiota may directly or indirectly contribute to1,30,31:

  • Loss of epithelial barrier integrity (increased permeability)
  • Immune dysfunction of the GI tract
  • Disrupted development and function of central and enteric nervous systems

Additionally, an increased number and/or type of bacteria in the upper GI tract (small intestinal bacterial overgrowth [SIBO]) has been associated with IBS, though data have been conflicting32

Gut microbiota dysbiosis

Gut infection/inflammation

Approximately 10% of IBS cases are thought to be due to a GI infection, often referred to as post-infectious IBS33,34; such infections include:

  • Bacterial dysentery35,36
  • Viral gastroenteritis37
  • Helminth (Giardia) infection38

Infections can result in mucosal low-grade inflammation,39,40 as well as an altered gut microbiota and bile acid malabsorption41

These pathophysiologic factors may contribute to varying degrees in different patients with IBS, but ultimately lead to the same core mechanisms, which subsequently result in symptoms of IBS

Altered gut motility

Motor abnormalities, such as increased frequency and irregularity of luminal contractions in the gut, have been observed in IBS42

Patients with IBS-C can experience prolonged colonic transit time, resulting in constipation43,44

In IBS-D, colonic motility may be accelerated, resulting in loose or watery stools and more frequent bowel movements45

Visceral hypersensitivity

Receptors on afferent and efferent nerve fibers that contribute to visceral pain perception have been identified in IBS45

  • Transient receptor potential channels (TRP channels)
  • Opioid receptors
  • Cannabinoid receptors

Patients with IBS have a heightened awareness of bowel distention and bloating46,47

Altered central perception

Alterations of brain networks may result in heightened awareness of gut symptoms, such as chronic abdominal pain, as well as contributing to anxiety, poor coping, and the conscious “gut feeling”2

Patients with IBS may experience exaggerated neuroendocrine responses and visceral perception during stress48,49

Enhanced pain perception may be due to altered central pain modulation circuits in various networks of the brain2,50

Learn more about IBS

References

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