La dépression, un sentiment qui prend aux tripes : le microbiome intestinal comme médiateur de la perturbation de l'épigénome intestino-vago-cérébral dans la dépression

 

Sarah Barnett-Burns

Université McGill

 

Domaine : neurosciences, santé mentale et toxicomanies

Programme Formation de doctorat

Concours 2018-2019

Partenaire :

Crohn's et colite Canada

We live our lives engaged in a biochemical conversation with trillions of intestinal microbes. It is known that this gut ‘microbiota' can modulate the intestines, and that neurons in our intestine can ‘talk' to neurons in our brain along the vagus nerve, as part of a larger bidirectional signaling system called the gut-brain axis. Recent research has suggested that microbial signals can be transmitted up the gut-brain axis to modulate mood, and may be a factor in the development of mental illnesses, such as depression. However, the exact mechanisms by which the gut microbiome alters gut-brain signaling and depression risk are still unclear.

Depression has been associated with disrupted stress response pathways. Gene regulatory processes known collectively as epigenetic mechanisms have been shown to be key mediators in this disruption. Interestingly, gut bacteria produce many of the chemicals that epigenetic processes require, and changes in the levels of these chemicals in mice have been associated with specific epigenetic changes in host cells. Thus, the gut microbiome may be an important epigenetic modulator. In addition, since some of the gut microbiota-associated mood alterations disappear in animals if the vagus nerve is severed, I hypothesize that gut microbiome mediated epigenetic processes increase depression risk in humans by altering neurons along the gut-vagal-brain axis. 

My PhD project will identify depression-associated changes in epigenetic regulators in the gut microbiomes of a) depressed people who died by suicide b) clinically depressed populations, and c) a mouse model of depression. I will test whether specific gut microbe species predict the epigenetic changes in neurons along the gut-vagal-brain pathway. As the first investigation of the gut-microbiome-brain epigenome, this project will further our understanding of microbial-host interactions, which may be a factor in multiple other diseases and an important target for future interventions.