Gutsy Moves: The Amygdala as a Critical Node in Microbiota to Brain Signaling

Abstract

The amygdala is a key brain area regulating responses to stress and emotional stimuli, so improving our understanding of how it is regulated could offer novel strategies for treating disturbances in emotion regulation. As we review here, a growing body of evidence indicates that the gut microbiota may contribute to a range of amygdala-dependent brain functions from pain sensitivity to social behavior, emotion regulation, and therefore, psychiatric health. In addition, it appears that the microbiota is necessary for normal development of the amygdala at both the structural and functional levels. While further investigations are needed to elucidate the exact mechanisms of microbiota-to-amygdala communication, ultimately, this work raises the intriguing possibility that the gut microbiota may become a viable treatment target in disorders associated with amygdala dysregulation, including visceral pain, post-traumatic stress disorder, and beyond. Also see the video abstract here: https://youtu.be/O5gvxVJjX18

The gut microbiota mediates reward and sensory responses associated with regimen-selective morphine dependence

“…Symbiotic bacteria from the indigenous gut microbiota contribute to the development and function of microglia in the brain, and perturbations in the gut microbiota are associated with abnormal microglial reactivity [13,14]. Changes in the gut microbiota are also associated with alterations in host behaviors and psychological disorders, including depression and anxiety [15]. Fecal samples isolated from depressed patients showed significant alterations in gut flora compared to healthy controls [16].…”

Early‐life stress leads to sex‐dependent changes in pubertal timing in rats that are reversed by a probiotic formulation

“…Given the links between altered pubertal timing and psychopathology, the identification of treatments that prevent such shifts in puberty onset may be clinically relevant to reduce long‐term mental health risk. In the present study, a gut–brain axis approach to this problem was assessed, targeting the microbiota (the collection of microorganisms residing within the gastrointestinal tract; Cowan, Callaghan, Kan, & Richardson, ; Cowan et al, ; Foster, Rinaman, & Cryan, ). Recent work has shown that sex differences in the microbiota emerge around puberty and the composition of the microbiota affects the levels of key sex hormones such as testosterone (Markle et al, ).…”

Mast Cells, Stress, Fear and Autism Spectrum Disorder

“…Triggers of mast cells can reach the hypothalamus from the nasal cavity through the cribriform plexus [99], or through the brain lymphatics [100]. Alternatively, mast cell-derived mediators, especially cytokines [101,102], can increase the permeability of the gut-blood barrier [103] and the BBB [57,104,105], allowing toxins to cross into the brain, activating microglia [38,95] and disrupting neuronal connectivity, especially in the amygdala [39,106,107].…”

“…Triggers of mast cells can reach the hypothalamus from the nasal cavity through the cribriform plexus [99], or through the brain lymphatics [100]. Alternatively, mast cell-derived mediators, especially cytokines [101,102], can increase the permeability of the gut-blood barrier [103] and the BBB [57,104,105], allowing toxins to cross into the brain, activating microglia [38,95] and disrupting neuronal connectivity, especially in the amygdala [39,106,107].Immune-neural connections regulate responses to environmental and infectious agents, leading to altered behavior [108]. Environmental triggers have been implicated in ASD [17,[109][110][111][112], including air pollutants [113,114], and a variety of pathogens [103].…”