Oral Enrichment of Streptococcus and its Role in Systemic Inflammation Related to Monocyte Activation in Humans with Cocaine Use Disorder

Xiaoyu Fu, Da Cheng, Zhenwu Luo, Amanda Wagner, Sylvia Fitting, Xiaomei Cong, Wanli Xu, Kendra Maas, Zhuang Wan, Jian Zhu, Zejun Zhou, William W. Stoops, Aimee McRae-Clark, Wei Jiang

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Cocaine use is commonly associated with increased chronic systemic inflammation. However, the drivers for cocaine use-mediated systemic inflammation are not fully understood. In the current study, we recruited individuals with cocaine use disorder and healthy individuals who did not use cocaine and collected paired saliva and blood samples. The saliva samples were used to assess the oral microbiome, and the plasma samples were evaluated for 33 cytokines and chemokines. Cocaine users exhibited decreased saliva microbial diversities compared to non-users. Streptococcus was the only increased genus in the saliva from cocaine users, whereas several genera were decreased in cocaine users compared to non-users. Notably, cocaine users exhibited increased plasma levels of several monocyte activation markers, including monocyte chemoattractant protein (MCP)-4, macrophage inflammatory protein (MIP)-3α, macrophage-derived chemokine (MDC), and thymus and activation-regulated chemokine (TARC), all of which were correlated with increased saliva levels of three Streptococcus species. Furthermore, treatment with Streptococcus or its lipoteichoic acid preferentially activated primary human monocytes to produce proinflammatory cytokines and chemokines, such as MIP-3α and TARC, in vitro compared to controls. However, monocytes failed to produce these chemokines after exposure to cocaine or cocaine plus bacteria compared to medium or bacteria alone. This study revealed that chronic cocaine use-associated inflammation in the blood may result from increased oral Streptococcus and its effects on myeloid cell activation, but does not result from cocaine directly. Graphical abstract: [Figure not available: see fulltext.]

Original languageEnglish
Pages (from-to)305-317
Number of pages13
JournalJournal of NeuroImmune Pharmacology
Issue number1-2
StatePublished - Jun 2022

Bibliographical note

Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.


  • Cocaine use disorder
  • Monocyte activation
  • Plasma inflammation
  • Saliva microbiome
  • Streptococcus

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Immunology and Allergy
  • Immunology
  • Pharmacology


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