DGBI are characterized by the presence of a variety of chronic, typically episodic symptoms attributed to the gastrointestinal tract in the absence of an underlying histological, biochemical, or physiological mechanism that consistently explains the symptoms. Several putative pathophysiological mechanisms have been proposed, including disordered motility, visceral hypersensitivity, low-grade inflammation, altered microbiota, immune activation, adverse reactions to foods and central nervous system dysfunction (which may or may not be related to psychological dysfunction), etc. Despite the fact that these disturbances have been reported in patients with DGBI, their relevance to symptom generation remains the subject of debate, in part because of the absence of a clearly established causal or even temporal relationship between symptoms and observed abnormal function, as well as the lack of treatments to specifically target the putative underlying mechanisms.

Several cross-sectional studies attempting to correlate symptoms with pathophysiological mechanisms in DGBIs have been criticized because they failed to explain a given symptom in all patients, or because of an inability to rule out other contributing mechanisms. The assessment of the nature and the severity of symptoms in DGBI depends on patient self-reports, which often lacks specificity and sensitivity. In addition, it is often assumed that DGBIs consist of subgroups with heterogeneous symptoms and different underlying pathophysiology. The Rome criteria have made this explicit for some (e.g. stool pattern-based IBS subtypes; EPS and PDS for functional dyspepsia) but not all DGBIs.

Researchers involved in pathophysiological studies have proposed many mechanisms underlying DGBI and used variable arguments and observations to support the relevance of these individual candidate mechanisms. To advance the field there is a need to identify the level of relevance of such putative pathophysiological processes, as this would enhance the knowledge and may prioritize target for therapeutic innovation or optimization.

In 2017, a group of international experts including some Rome Board members developed plausibility criteria for mechanisms in functional gastrointestinal disorders and published these as a paper in Gut. The plausibility criteria are based on aspects such as presence, temporal association, correlation between level of impairment and symptom severity, induction in healthy subjects and treatment response or congruent natural history. In addition, a plausibility numerical score was proposed, based on the strength of evidence. In the paper, the plausibility criteria were applied to 4 specific mechanisms in 3 different functional disorders.

There is a clear opportunity to approach the various DGBIs and the proposed underlying mechanisms in a systematic fashion. In case of IBS, for instance, the plausibility of altered fecal microbiota composition, or increased mucosal permeability, or anxious co-morbidity as mechanism underlying symptom generation could be assessed. There are similar examples for each putative pathophysiological mechanism in each DGBI. This approach will provide a novel and critical review of our current DGBI disease concepts and establish the areas of knowledge and uncertainty.