Robert Turell Professor of Medical Microbiology and Immunology And Department Chair

University of Wisconsin | LIVESTREAM

Gut-microbiota membership is associated with diverse neuropsychological-diseases, including substance use disorders (SUDs). Unravelling mechanistic interactions between gut microbes and the host during psychostimulant use remains challenging. Here we show that cocaine exposure increases intestinal levels of norepinephrine, sensed through the bacterial adrenergic receptor QseC to promote virulence and intestinal colonization of C. rodentium (a murine pathogen used as a surrogate animal model for EHEC), as well as intestinal colonization of commensal g-Proteobacteria. This shift in microbiota-composition depletes the neuroactive metabolite glycine (used as a nitrogen source by C. rodentium and/or g-Proteobacteria) in the gut and cerebrospinal fluid, enhancing host cocaine-induced behaviors. Glycine repletion reversed this response, and intestinal colonization by g-Proteobacteria unable to uptake glycine did not alter the host response to cocaine. Transcriptomic profiling indicates a role of microbiota modulated glycine levels in cocaine induced transcriptional plasticity in the nucleus accumbens through the glutamatergic transmission. Altogether, we introduce a mechanism by which intestinal bacteria alter the host’s brain responses to cocaine that could be exploited to modulate reward-related brain circuits that contribute to SUDs.

Host: Dr. Marvin Whiteley