Figure 1.

Bidirectional interactions within the brain gut microbiome (BGM) system are modulated by diurnal oscillations. Outputs generated by the central autonomic brain network modulate the activity of various components of the gut connectome (immune, endocrine, epithelial cells, gap junctions, smooth muscle, neurons) which influence gut function and interactions of the gut with the microbiome. Sympathetic nervous system outflow from the brain can also modulate gut microbial gene expression and function directly. Both gut and brain induced modulation of gut microbial metabolites and secretion of neuroactive neuroactive and inflammatory signaling molecules feed back to the brain and modulate the activity of brain networks. Diurnal variations (depicted by an oscillating line), food intake, sleep and physical activity modulate autonomic nervous system (ANS) activity as well as gut microbial composition and function. Oscillations between the brain and the gut are synchronized with the central clock in the hypothalamic suprachiasmatic nucleus. Modified with permission from Osadchiy et al. [21] and Chaix et al. [22].