Gut colonization by Proteobacteria alters host metabolism and modulates cocaine neurobehavioral responses

CUESTA SANTIAGO; BURDISSO PAULA; SEGEV AMIR; KOURRICH SAÏD; SPERANDIO VANESSA

CELL HOST & MICROBE

CELL PRESS

Lugar: United States; Año: 2022

1931-3128

Gut-microbiota membership is associated with diverse neuropsychological outcomes, including substance use disorders (SUDs). Here, we use mice colonized with Citrobacter rodentium or the human g-Proteobacteria commensal Escherichia coli HS as a model to examine the mechanistic interactions between gut microbes and host responses to cocaine. We find that cocaine exposure increases intestinal norepinephrine levels that are sensed through the bacterial adrenergic receptor QseC to promote intestinal colonization ofg-Proteobacteria. Colonized mice show enhanced host cocaine-induced behaviors. The neuroactive metabolite glycine, a bacterial nitrogen source, is depleted in the gut and cerebrospinal fluid of colonized mice. Systemic glycine repletion reversed, and g-Proteobacteria mutated for glycine uptake did not alter the host response to cocaine. g-Proteobacteria modulated glycine levels are linked to cocaine-induced transcriptional plasticity in the nucleus accumbens through glutamatergic transmission. The mechanism outlinehere could potentially be exploited to modulate reward-related brain circuits that contribute to SUDs.