Gut-brain and brain-gut interconnectedness and what it can tell us about association between psychiatric illness and functional GI disorders – observed for many decades but mechanisms and directionality are still under research

2015 review article from Australian group discusses this, focusing on microbial envt of gut and impact of early trauma on brain-gut communication.

Bi-directionality:o 12 yr prospective study: anxiety and depression predict onset of FGID at 12 yr and vice

versa – FGID predicts onset of anxiety/depression o 5 yr f/u study from UK: of patients who recorded a FGID and a mood diagnosis over

the course of the 5 years, two thirds had a psychological diagnosis first, versus one third having a FGID diagnosis first

Brain-gut:o ANS regulates ENS. Anxiety/depression increased sympathetic tone, decreased

parasympathetic tone, which alter gut motility, secretion and immune function Noradrenaline rapid bacterial growth and translocation into gut wall more

inflammation o HPA axis upregulation CRF directly increases GI motility, secretion and sensitivity.

CRF upregulated in IBS and stress states. Cortisol mediates inflammation/cytokines downstream which affect GI function and microbial envt.

o responsiveness of many FGID to brain orientated therapies like CBT, altered sensitivity to rectal distension in IBS sufferers that improves with therapy or anti-depressants

Gut-brain: o infection leads to excessive TNF-α and other cytokine production in vulnerable

individuals. TNF-α causes anxiety in animals and depression in humans fits with dysbiosis theory (gut flora alteration) of IBS independent from known detrimental effect of chronic illness on sense of self,

relationships, and lifestyle resulting inflammation from infection can affect absorption of neuroactive

substances produced by bacteria, bacterial translocation into gut wall, and release of serotonin by GI neuroendocrine cells, increased peripheral pain sensitivity

inflamm cytokines can affect neurogenesis and neuron branching in hippocampus

Early trauma and brain-gut axiso Maternal separation models in mice have demonstrated not only behavioural and

neurochemical changes, but also some reversal from probiotic use. Mice separated from moms 3 hrs/day, forced swim test to measure despair, Bifidobacterium infantis (a probiotic used in IBS) normalisation of noradrenaline in the brainstem and peripheral IL-6 levels, and improvements in the forced swim test

Why significant?o Authors hypothesize that IBS is more commonly a result of a brain-gut disorder rather

than gut-brain (may be similar patterns in other FGIDs), and distinguishing between these groups would have therapeutic implications and may explain why only a subset with IBS for example respond to psychological interventions or antidepressants and others are resistant

o Patients are more amenable to take dietary/probiotic therapy than psychiatric treatments, so more research is needed to determine if such treatments could prevent progression of FGID and anxiety/depression