Irritable Bowel Syndrome: Causes

Pathogenesis (development of disease)

To date, no definitive cause for irritable bowel syndrome (IBS) has been found. Until now, it has held that most patients have a lower-than-normal pain threshold in the bowel, which is referred to as hyperalgesia (excessive sensitivity to pain and response to a usually painful stimulus). Hyperalgesia had been consistently demonstrated in studies as the only factor in the development of irritable bowel syndrome. It has since been demonstrated that irritable bowel is less sensitive. It is possible that the intestinal wall of these patients is apparently desensitized by an originally too strong activation.Furthermore, an increased motor activity in the colon, increased gas reflux into the stomach and a strongly prolonged transit time of food through the intestine are discussed. In about a quarter of irritable bowel patients, the disease was preceded by bacterial gastroenteritis (so-called post-infectious IBS); associated with this is possibly an alteration of the intestinal flora (dysbiosis) [in 7-36% of patients]. Furthermore, a personal predisposition (genetic factors as well as learned behavioral patterns) as well as psychological factors (traumatic events), psychological comorbidities (depression, anxiety, etc.) and stress are discussed. Pathophysiologically relevant molecular and cellular factors that may be involved in IBS:

  • Disorders of the hypothalamic-pituitary-adrenocortical axis.
  • Disorders of the autonomic and enteric nervous systems.
  • Microstructural abnormalities as well as altered signal processing in different brain areas.
  • Reduced parasympathetic activity, i.e., sympathetic overactivation, which. may be related to increased stress levels.
  • Influence of hormonal status: higher estrogen levels are associated with reduced intestinal motility.
  • Motility disorders (increased or reduced transit time; increased gas production) and altered intestinal-intestinal reflexes (stretching of the descending colon/descending colon showed irritable bowel patients increased colonic motility/colon motility compared to healthy individuals).
  • Altered sensitivity (lowered pain threshold): in most cases, there is visceral (“intestinal”) hypersensitivity
  • Impaired bile acid metabolism: up to 15% of IBS-O patients have a low concentration of total bile acids and a reduced deoxycholic acid concentration in the stool.
  • Disturbances of intestinal flora (dysbiosis) and mucosal permeability (decreased tissue resistance and barrier function).
  • Immune mediators in mucosal biopsies (increased release of: Defensins, histamine, proteases, tryptase and cytokines).
  • Immune mediators in blood (increased levels of ACTH and cortisol).
  • Immune cells in mucosal biopsies (mast cells, intraepithelial T cells).
  • Serotonin metabolism (increased serotonin plasma levels).
  • Cellular changes after infection (e.g., increased mast cell count, increased intraepithelial lymphocytes).
  • Alteration of protease-mediated functions: increased protease concentrations (serine proteases) have been measured in the stool of RDS-D patients
  • Altered fatty acid pattern in stool: the difference between propionic acid and butyric acid in stool has biomarker quality with a sensitivity of 92% and a specificity of 72%; slightly increased lactoferrin levels.
  • Epigenetic factors may be involved in the genesis of IBS; these include traumatic experiences, psychological and psychological stress, etc.

Current consensus is: IBS patients have disorders of intestinal barrier, motility, secretion and/or visceral sensitivity.

Etiology (Causes)

Biographic causes

  • Genetic burden – a genetic predisposition to IBS exists.
    • A genome-wide association study (GWAS) indescribes a risk gene on chromosome 9q31.2 (gene variant rs10512344) that primarily favors the obstipation-predominant type. The association was found only in female patients.

Behavioral causes

  • Nutrition
    • Micronutrient deficiency (vital substances) – see Prevention with micronutrients.
  • Psycho-social situation
    • Acute and chronic stress
    • Psychological stress

Causes related to disease

  • Gastroenteritis (stomach flu).
    • Gastrointestinal infections – regardless of their cause, an irritable bowel diagnosis was significantly more common during the following five years
    • Infection with Clostridium difficile in the sense of postinfectious IBS.
  • Food allergy
  • Food intolerances (50-70% of cases versus normal population: 20-25%).
  • Psychological pre-existing conditions (risk increase 70%).
  • Post-traumatic stress (risk increase fivefold).

Laboratory diagnoses – laboratory parameters considered independent risk factors.

Medicines

  • Previous antibiotic therapy can be a trigger of IBS.