Objective Psychological factors are known to be associated with functional gastrointestinal disorders (FGIDs) including irritable bowel syndrome (IBS) and functional dyspepsia (FD). No prospective studies have evaluated whether it is the brain (eg, via anxiety) that drives gut symptoms, or whether gut dysfunction precipitates the central nervous system features such as anxiety. In a 12-year longitudinal, prospective, population-based study, we aimed to determine the directionality of the brain–gut mechanism in FGIDs. Design Participants (n=1775) were a random population sample from Australia who responded to a survey on FGIDs in 1997 and agreed to be contacted for future research; 1002 completed the 12-year follow-up survey (response rate =60%), with 217, 82 and 45 people meeting Rome II for new onset FGIDs, IBS and FD, respectively. Anxiety and depression were measured using the Delusions Symptom States Inventory at baseline and follow-up. Results Among people free of a FGID at baseline, higher levels of anxiety (OR 1.11; 95% CI 1.03 to 1.19, p=0.006) but not depression at baseline was a significant independent predictor of developing new onset FGIDs 12 years later. Among people who did not have elevated levels of anxiety and depression at baseline, those with a FGID at baseline had significantly higher levels of anxiety and depression at follow-up (mean difference coefficient 0.76, p<0.001 and 0.30, p=0.01 for anxiety and depression, respectively). In IBS higher levels of anxiety and depression at baseline were predictive of IBS at follow-up, while only depression was predictive of FD at follow-up. Conclusions The central nervous system and gut interact bidirectionally in FGIDs.

Summary: Background: Traditionally, functional gastrointestinal disorders (FGIDs) are conceptualised as originating in the brain via stress pathways (brain‐to‐gut). It is uncertain how many with irritable bowel syndrome (IBS) and functional dyspepsia (FD) have a gut origin of symptoms (gut‐to‐brain pathway).Aims: To determine if there is a distinct brain‐to‐gut FGID (where psychological symptoms begin first) and separately a distinct gut‐to‐brain FGID (where gut symptoms start first).Methods: A prospective random population sample from Newcastle, Australia who responded to a validated survey in 2012 and completed a 1‐year follow‐up survey (n = 1900). The surveys contained questions on Rome III IBS and FD and the Hospital Anxiety and Depression Scale.Results: We found that higher levels of anxiety and depression at baseline were significant predictors of developing IBS (OR = 1.31; 95% CI 1.06–1.61, P = 0.01; OR = 1.54; 95% CI 1.29–1.83, P < 0.001) and FD (OR = 1.28; 95% CI 1.05–1.55, P = 0.01; OR = 1.55, 95% CI 1.32–1.83, P < 0.001), respectively, at the 1‐year follow‐up. Among those people who did not have elevated levels of anxiety and depression at baseline, subjects at baseline with documented IBS (mean difference 0.34; 95% CI 0.13–0.55, P = 0.002; 0.81; 95% CI 0.47–1.15, P < 0.001) and FD (0.38; 95% CI 0.14–0.63, P = 0.002; 0.92; 95% CI 0.57–1.27, P < 0.001), reported significantly higher levels of anxiety and depression at the 1‐year follow‐up. We calculated in one‐third of individuals a mood disorder precedes FGID but in two‐thirds an FGID precedes the mood disorder.Conclusion: While brain–gut pathways are bidirectional, a major subset begin with gut symptoms first and only then psychological distress develops, implicating primary gut mechanisms as drivers of the gut and extra‐intestinal features in many cases.