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Aliment Pharmacol Ther. 2016 Sep;44(6):592-600. doi: 10.1111/apt.13738. Epub 2016 Jul 22.

Evidence that independent gut-to-brain and brain-to-gut pathways operate in the irritable bowel syndrome and functional dyspepsia: a 1-year population-based prospective study.

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Faculty of Health & Medicine, University of Newcastle, Newcastle, NSW, Australia.
Department of Psychology, Macquarie University, North Ryde, NSW, Australia.



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).


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).


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.


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.


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.

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