A holistic view of the pathogenesis of irritable bowel syndrome (IBS)

Irritable bowel syndrome (IBS) is thought to be caused by various pathophysiological mechanisms, which have not yet been clearly identified or explained. Changes in the gut microbiome, mild inflammatory processes in the intestinal mucosa, and functional disorders of the intestine are thought to play a central role in the pathophysiology of irritable bowel syndrome.

Patients with irritable bowel syndrome (IBS) have been reported to have disturbances in small and large intestine gastrointestinal motility, i.e., colonic transit time is either accelerated or slowed down. Disturbances in the microbiome and bacterial dysbiosis of the small intestine have also been documented. Compared to healthy controls, irritable bowel syndrome (IBS) sufferers have a different composition of the microbiome in the intestine in terms of both quality and quantity. In fecal samples, elevated levels of lactobacilli, propionic acid, and acetic acid were measured on the one hand, and reduced concentrations of bifidobacteria on the other.

Abnormal serotonin concentrations in the intestinal gastrointestinal tract can disrupt the regulation of the central nervous system (CNS) and trigger an increased stress response and increased pain perception in the abdominal area. The increased innervation of the intestinal mucosa results in sympathetic activation. Increased sympathetic activity could cause higher stress levels. However, a clear causal link between psychological stress and the development of irritable bowel syndrome (IBS) in adults has not been established: Stress is, however, a possible cofactor in the development or maintenance of symptoms.

Psychological stress and childhood trauma

Irritable bowel syndrome and mental illnesses such as anxiety and depression are often linked and can reinforce each other. Mechanistically, activation induced by psychological stress of the hypothalamic-pituitary-adrenal axis (hypothalamic-pituitary-adrenal (HPA) axis) and the autonomic nervous system, mediated by increased release of corticotropin-releasing hormone (corticotropin-releasing hormone (CRH)), is discussed. These processes influence intestinal gastrointestinal motility and increase visceral hypersensitivity.

Colonoscopies of affected individuals have revealed altered mucosal permeability. The colonic mucosa shows increased proteolytic activity, which is attributable to the activation of trypsin. This leads to more intensive degradation of the tight junction-associated protein occludin and increased mucosal permeability. The altered mucosal mediator profile causes activation of the enteric nervous system, leading to increased density of nerve fibers. The increased spinal transmission of intestinal stimuli intensifies the activation of centers in the CNS. The intestine can thus become "hyperpermeable," also known as increased intestinal permeability.

Consequences of disturbed intestinal flora

Leaky gut syndrome impairs the protective function of the intestinal mucosa, making the intestinal barrier more hyperpermeable. Recent studies show that this impaired barrier function occurs more frequently in patients with irritable bowel syndrome and can be considered a possible pathophysiological factor.

Symptoms can include the following:

• Flatulence
• Gas
• Cramp-like abdominal pain

Numerous studies suggest that hormonal differences between men and women could be a connecting mechanism. Progesterone in particular influences the 5-hydroxytryptamine (5-hydroxytryptamine (5-HT)) system, which plays a central role in controlling intestinal peristalsis. In addition, both estrogen and progesterone have an inhibitory effect on the contraction of smooth muscles in the intestine.

These hormonal effects could explain why the constipation-dominant form of irritable bowel syndrome (irritable bowel syndrome (IBS)-C) is more common in women than in men.