Microbiota-gut-brain messengers: The effects of short chain fatty on stress sensitivity

The short chain fatty acids (SCFA), acetate, propionate and butyrate, are major bacterial metabolites resulting from carbohydrate fermentation in the colon. They are hypothesized to affect brain function through immune, endocrine, vagal and other humoral pathways. However, their exact mechanisms of action remain to be established. We previously showed that administration of a SCFA mix for 1 week to healthy males reduces the cortisol response to psychosocial stress and thus may be helpful in the prevention and/or treatment of mood disorders. This proposal builds on these promising results. In an observational study, we will evaluate whether a subject’s microbiota composition predicts its sensitivity to stress. Furthermore, we will perform 3 intervention studies in which known amounts of SCFA will be administered to the colon using capsules with a colon delivery coating to evaluate putative mechanisms of action. First, we will investigate whether the effects of SCFA on stress are mediated by epigenetic mechanisms (inhibition of histone deacetylases) using innovative PET-MR imaging. In a second study, the impact of systemic inflammation onstress will be assessed after which we will evaluate whether SCFA will counteract inflammationinduced stress response. Targeting the intestinal microbiota and SCFA production may provide a new target in the management of stress and mood disorders.