Irritable bowel syndrome
A holistic view of the pathogenesis of irritable bowel syndrome (IBS)
The exact pathogenesis of irritable bowel syndrome (IBS) is currently unclear. It is a complex condition caused by the interaction of biological, psychosocial and environmental factors. The involvement of the gut-brain axis requires a holistic approach to research and treatment.
athophysiological diversity in irritable bowel syndrome
Within irritable bowel syndrome (IBS) , various pathophysiological mechanisms are discussed, but these have not yet been clearly or conclusively clarified. 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.
The role of the gut-brain axis
The Rome IV criteria were the first to establish a framework describing irritable bowel syndrome as a disorder of the gut-brain axis. The cause of this disorder may lie in the brain, the gut or in faulty communication between the two systems.
Imaging techniques show abnormal brain reactions in affected individuals, indicating changes in cognitive processes. Studies also show that dysregulation of the hypothalamic-pituitary-adrenal axis (HPA axis) and chronic stress can impair cognitive abilities.
In addition, mood disorders, chronic pain and altered gut flora are associated with cognitive deficits, particularly in the areas of attention and memory. These findings support the assumption that IBS should primarily be understood as a disorder of the gut-brain axis, in which the brain plays a central role in the development and maintenance of symptoms.
Altered intestinal motility and gut flora composition
Patients with IBS have been reported to have disturbances in small and large intestine motility, i.e. colon 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, IBS sufferers have a different composition of the microbiome in the intestine in terms of both quality and quantity. In stool samples, elevated levels of lactobacilli, propionic acid and acetic acid were measured on the one hand, and reduced concentrations of bifidobacteria on the other.
Immunological dysregulation
IBS is often associated with a disturbance of the enteral immune balance. Microinflammatory or neuroimmunological processes take place in the intestinal mucosa, leading to a local increase in various immune cells (e.g. mast cells, T lymphocytes). Stress can also cause chronic activation of the immune system. Mild inflammatory processes in the intestinal mucosa not only increase mast cell density but also histamine release.
Example: Acute gastroenteritis
In scientific literature, acute gastroenteritis is often discussed as a significant risk factor for the development of irritable bowel syndrome (IBS). There are several hypotheses regarding the mechanism behind this.
These include a long-term imbalance of immune cells and inflammation-modulating mediators, which can disrupt the inflammatory homeostasis of the intestine, impairment of the intestinal mucosal barrier, and a disturbed composition of the gut microbiome (intestinal dysbiosis).
What role do serotonin and stress axes play?
Abnormal serotonin levels in the 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 IBS in adults has not been established: stress as a cofactor in the development or maintenance of symptoms is possible, however.
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, stress-induced activation of the hypothalamic-pituitary-adrenal axis (HPA axis) and the autonomic nervous system, mediated by increased release of corticotropin-releasing hormone (CRH), is discussed. These processes influence intestinal motility and increase visceral sensitivity.
Irritable bowel syndrome and leaky gut: when the intestinal barrier fails
Colonoscopies of affected individuals have revealed altered mucosal permeability. The colonic mucosa shows increased protease activity, which is attributable to the activation of trypsin. This leads to more intensive degradation of the tight junction protein occludin and increased mucosal permeability. The altered mucosal mediator profile causes activation of the enteric nervous system, leading to nerve fibre densification. The increased spinal transmission of intestinal stimuli intensifies the activation of centres in the CNS. The intestine can thus become "permeable", also known as leaky gut.
Consequences of disturbed intestinal flora
Leaky gut syndrome impairs the protective function of the intestinal mucosa, making the intestinal barrier more permeable. 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
Hormonal modulation of intestinal function: Why IBS is more common in women
Numerous studies suggest that hormonal differences between men and women could be a connecting mechanism. Progesterone in particular influences the 5-hydroxytryptamine (5-HAT) system, which plays a central role in controlling intestinal peristalsis. In addition, both oestrogen and progesterone have an inhibitory effect on the contraction of smooth muscle in the intestine.
These hormonal effects could explain why the constipation-dominant form of irritable bowel syndrome (IBS-C) is more common in women than in men.
Sources
- Layer P et al. Update S3 guideline on irritable bowel syndrome: definition, pathophysiology, diagnosis and treatment. Joint guideline of the German Society for Gastroenterology, Digestive and Metabolic Diseases (DGVS) and the German Society for Neurogastroenterology and Motility (DGNM) – June 2021 – AWMF registration number: 021/016. Z Gastroenterol. 2021 Dec;59(12):1323-1415.
- Sulaimi F, Ong TSK, Tang ASP, Quek J, Pillay RM, Low DT, Lee CKL, Siah KTH, Ng QX. Risk factors for developing irritable bowel syndrome: systematic umbrella review of reviews. BMC Med. 2025 Feb 21;23(1):103. doi: 10.1186/s12916-025-03930-5. PMID: 39985070; PMCID: PMC11846330.
- Akbari R, Salimi Y, Dehghani-Aarani F, Rezayat E. Attention in irritable bowel syndrome: A systematic review of affected domains and brain-gut axis interactions. J Psychosom Res. 2025 Apr;191:112067. doi: 10.1016/j.jpsychores.2025.112067. Epub 27 February 2025. PMID: 40048890.