GUT MICROBIOTA CONTROL OF BRAIN RESPONSES TO STRESS

The gut microbiota strongly influences host physiology and behaviour, including the stress response. Studies in germ-free mice, revealed that in the absence of bacteria plasma levels of stress hormone corticosterone (CORT) are higher; also, behavioural studies showed that the gut microbiota composition affects stress susceptibility and resilience. However, the mechanisms underlying the communication between the gut microbiota and the brain remain underexplored. Unpublished data from our lab has revealed that gavage with muramyl dipeptide (MDP), a component of the bacterial cell wall, increases plasma CORT levels, and affects neuronal activity in the paraventricular nucleus (PVN) of the hypothalamus, a critical region in stress regulation. It has been shown also that neurons in the PVN express the pattern recognition receptor Nod2 that recognizes MDP. Those neurons may be part of a possible mechanism by which the microbiota affects stress response. Interestingly, our data shows a sex-bias in the influence of microbiota-derived compounds in the stress response. We revealed that only old female mice (8 months of age) increase plasma CORT in response to MDP. Removal of Nod2 from PVN neurons in old females induced behavioural alterations, including an abnormal response to stress. This study will contribute to a better understanding of the microbiota-gut-brain axis and possibly identify new targets for the treatment of stress disorders.