Figure 2.

Bidirectional interactions within the gut microbiota/brain axis [126]. A network of specialized target/transducer cells in the gut wall functions as an interface between the microbiota and the host lumen. In response to external and bodily demands, the brain modulates these specialized cells within this network via the branches of the ANS (sympathetic and parasympathetic/vagal efferents) and the HPA axis. Such modulation can be transient, such as in response to transient perturbations, or long lasting such as in response to chronically altered brain output. The microbiota are in constant bidirectional communication with this interface via multiple microbial signaling pathways, and this communication is modulated in response to perturbations of the microbiota or the brain. The integrated output of the gut microbial–brain interface is transmitted back to the brain via multiple afferent signaling pathways including the endocrine (metabolites, cytokines, and microbial signaling molecules) and neurocrine (vagal and spinal afferents). While acute alterations in this interoceptive feedback can result in transient functional brain changes (GI infections), chronic alterations are associated with neuroplastic brain changes. Potential therapies aim to normalize altered microbiota signaling to the ENS and central nervous system. ECC, enterochromaffin cells; FMT, fecal microbial transplant; ICC, interstitial cell of Cajal; SCFA, short-chain fatty acid; SMC, smooth muscle cell.