Cocaine Induces Inflammatory Gut Milieu by Compromising the Mucosal Barrier Integrity and Altering the Gut Microbiota Colonization

Ernest T. Chivero, Rizwan Ahmad, Annadurai Thangaraj, Palsamy Periyasamy, Balawant Kumar, Elisa Kroeger, Dan Feng, Ming Lei Guo, Sabita Roy, Punita Dhawan, Amar B. Singh, Shilpa Buch

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Abstract

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, we sought to understand the causal association between CUD and gut dysbiosis. Using a comprehensive approach, we 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, our 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.

Original languageEnglish (US)
Article number12187
JournalScientific reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

ASJC Scopus subject areas

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    Chivero, E. T., Ahmad, R., Thangaraj, A., Periyasamy, P., Kumar, B., Kroeger, E., Feng, D., Guo, M. L., Roy, S., Dhawan, P., Singh, A. B., & Buch, S. (2019). Cocaine Induces Inflammatory Gut Milieu by Compromising the Mucosal Barrier Integrity and Altering the Gut Microbiota Colonization. Scientific reports, 9(1), [12187]. https://doi.org/10.1038/s41598-019-48428-2