Cocaine use disorder (CUD), a major health crisis, has traditionally been considered a complication of the CNS; however, it is also closely associated with malnourishment and deteriorating gut health. In light of emerging studies on the potential role of gut microbiota in neurological disorders, researchers from the University of Nebraska Medical Center sought to understand the causal association between CUD and gut dysbiosis. Using a comprehensive approach which included 16S gene sequencing, they confirmed that cocaine administration in mice resulted in alterations of the gut microbiota. Furthermore, cocaine-mediated gut dysbiosis was associated with upregulation of proinflammatory mediators including NF-κB and IL-1β. In vivo and in vitro analyses confirmed that cocaine altered gut-barrier composition of the tight junction proteins while also impairing epithelial permeability by potentially involving the MAPK/ERK1/2 signaling. Taken together, these findings unravel a causal link between CUD, gut-barrier dysfunction and dysbiosis and set a stage for future development of supplemental strategies for the management of CUD-associated gut complications.
Cocaine-administration in mice induced gut dysbiosis
Wild-type mice (C57BL/6) were administered cocaine (i.p, 20 mg/kg) or saline for seven consecutive days followed by euthanasia within 1 hr of the last injection. Fecal droppings and distal colon fecal matter were collected for 16S-rRNA sequencing. Several bacterial genus OTUs were altered in the presence of cocaine compared with controls as shown by the stacked bar (A) and the heat map (B) in pooled samples for each group. Cocaine administration affected microbial composition as shown by relative abundance of 16S rRNA transcripts in each individual animal at the genus level (C). UPGMA weighted unifrac and principal coordinates analysis (multidimensional scaling, MDS) show the clustering of microbiota from cocaine-administered mice (D,E respectively). S = Saline, C = cocaine, c = colon, d = droppings, col = colon, drop = droppings. n = 10/group.
Chivero ET, Ahmad R, Thangaraj A, Periyasamy P, Kumar B, Kroeger E, Feng D, Guo ML, Roy S, Dhawan P, Singh AB, Buch S. (2019) Cocaine Induces Inflammatory Gut Milieu by Compromising the Mucosal Barrier Integrity and Altering the Gut Microbiota Colonization. Sci Rep 9(1):12187. [article]