But also gastrointestinal motor dysfunction, viral or bacterial infection, modifications in intestinal permeability, dysmicrobism, dysregulation of the brain/intestinal axis, biliary acid malabsorption, psychological and genetic factors and low grade intestinal inflammation !

Several studies have revealed the presence of a microinflammatory or even proinflammatory state, both at the digestive and systemic levels.

• One epidemiological study of a cohort of patients presenting with acute gastroenteritis after food contamination demonstrated that this group ran a high risk of having IBS within a year or two after that infectious episode.
• Numerous studies on intestinal flora have revealed dysmicrobism in patients with IBS.
• Samplings taken from patients with IBS have frequently revealed infiltration of the mucosa by lymphocytes and polynuclear cells, and increased mastocyte levels. These cells release a certain number of substances, among them interstitial proinflammatory substances, which participate in sensitizing nerve endings of the digestive tract. In this group of patients, following that inflammatory episode, an increase in digestive permeability was observed which favored passage of macromolecules and bacteria which then perpetuated the inflammatory state.

While visceral hypersensitivity is recognized as an important characteristic, the processes underlying such hypersensitivity remain mysterious.

Several neurological mechanisms would appear to enter into action. The inflammatory reaction might also modify the stimulation threshold of certain sensitive neurons. Visceral hypersensitivity could be due to either: 1) sensitization of neurons located in the digestive wall; 2) a central origin, via hyperexcitation of neurons located in the spinal cord (posterior horn), amplifying sensitive messages of digestive origin; or 3) difficulty in integrating these messages by the central nervous system.

The psychological state interferes with perception and integration of sensitive information of digestive origin, notably by maintaining alertness toward these stimuli. Stress could lead to release of substances favoring a pre-inflammatory state.

The discovery of these phenomena of visceral hypersensitivity and hyperexcitability of neurons of the posterior horn, favoring medullar hyperexcitability, sheds new light on our comprehension of pathologies associated with IBS and often poorly understood: fibromyalgia (49%), chronic fatigue syndrome (51%), dyspareunia, irritable bladder, etc.

As is the case with other inflammatory diseases the origins of which are unknown, genetic factors might be associated with IBS. Nevertheless, the expected benefits from setting up such studies (understanding of its physiopathology, diagnostic improvements, prediction of evolution, therapeutic responses) are minor.

Although our knowledge of the physiopathology of IBS has considerably increased, much of its mystery remains. Recently created experimental models are raising the hope of developing new molecules. Indeed, at present, a therapeutic benefit of only 10% exists compared to a placebo !