Mounting evidence suggests a link between gut microbiota abnormalities and post-traumatic stress disorder (PTSD). However, whether and how the gut microbiota influences PTSD susceptibility is poorly understood. Here using the arousal-based individual screening model we provide evidence for pre-trauma and post-trauma gut microbiota alterations in susceptible mice exhibiting persistent PTSD-related phenotypes. A more in-depth analysis revealed an increased abundance of bacteria affecting brain processes including myelination, and brain systems like the dopaminergic system. Because dopaminergic dysfunctions play a key role in the pathophysiological mechanisms subserving PTSD, we assessed whether this alteration in gut microbiota composition could be associated with abnormal levels of metabolites inducing dopaminergic dysfunctions. We found high levels of the L-tyrosine-derived metabolite p-cresol exclusively in the prefrontal cortex of susceptible mice. We further uncovered abnormal dopamine and DOPAC levels, together with a detrimental increase of dopamine D3 receptor expression, exclusively in the prefrontal cortex of susceptible mice. Conversely, we observed either resilience mechanisms aimed at counteracting these p-cresol-induced dopaminergic dysfunctions or myelination-related resilience mechanisms only in the prefrontal cortex of resilient mice. These findings reveal that gut microbiota abnormalities foster trauma susceptibility and thus it may represent a promising target for therapeutic interventions.

Gut microbiota alterations promote traumatic stress susceptibility associated with p-cresol-induced dopaminergic dysfunctions

Laudani, Samuele;Torrisi, Sebastiano A;Fuochi, Virginia;Furneri, Pio M;Drago, Filippo;Salomone, Salvatore;Tascedda, Fabio;Marco Leggio, Gian
2022-01-01

Abstract

Mounting evidence suggests a link between gut microbiota abnormalities and post-traumatic stress disorder (PTSD). However, whether and how the gut microbiota influences PTSD susceptibility is poorly understood. Here using the arousal-based individual screening model we provide evidence for pre-trauma and post-trauma gut microbiota alterations in susceptible mice exhibiting persistent PTSD-related phenotypes. A more in-depth analysis revealed an increased abundance of bacteria affecting brain processes including myelination, and brain systems like the dopaminergic system. Because dopaminergic dysfunctions play a key role in the pathophysiological mechanisms subserving PTSD, we assessed whether this alteration in gut microbiota composition could be associated with abnormal levels of metabolites inducing dopaminergic dysfunctions. We found high levels of the L-tyrosine-derived metabolite p-cresol exclusively in the prefrontal cortex of susceptible mice. We further uncovered abnormal dopamine and DOPAC levels, together with a detrimental increase of dopamine D3 receptor expression, exclusively in the prefrontal cortex of susceptible mice. Conversely, we observed either resilience mechanisms aimed at counteracting these p-cresol-induced dopaminergic dysfunctions or myelination-related resilience mechanisms only in the prefrontal cortex of resilient mice. These findings reveal that gut microbiota abnormalities foster trauma susceptibility and thus it may represent a promising target for therapeutic interventions.
2022
Animal model
Dopamine
Gut-brain axis
Microbiota
PTSD
Resilience
Stress
Susceptibility
p-cresol
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11769/541803
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