Opioid Use, Gut Dysbiosis, Inflammation, and the Nervous System

Abstract

Opioid use disorder (OUD) is defined as the chronic use or misuse of prescribed or illicitly obtained opioids and is characterized by clinically significant impairment. The etiology of OUD is multifactorial as it is influenced by genetics, environmental factors, stress response and behavior. Given the profound role of the gut microbiome in health and disease states, in recent years there has been a growing interest to explore interactions between the gut microbiome and the central nervous system as a causal link and potential therapeutic source for OUD. This review describes the role of the gut microbiome and opioid-induced immunopathological disturbances at the gut epithelial surface, which collectively contribute to OUD and perpetuate the vicious cycle of addiction and relapse.

Keywords: Enteric nervous system; Gut-brain axis; Microbiome; OUD; Opioids.

Fig. 1

Morphine treatment upregulates TLR expression in intestinal tissue. Increased TLR signaling in intestinal epithelial cells leads to MLCK induced tight junction redistribution and increase intestinal permeability. (Adapted and modified from Meng et al. 2013). (IEC, Intestinal epithelial cell)

Fig. 2

Opioid use and gut-brain axis: opioid induced gut dysbiosis leads to mucosal, systemic, and neuroinflammation which contributes to opioid associated comorbidities such as tolerance, dependence and withdrawal. (GDNF, glia derived neurotropic factor; SCFA, short-chain fatty acid; BA, bile acid; ACh, Acetylcholine; VIP, vasoactive intestinal polypeptide; NO, nitric oxide; ENS, enteric nervous system; MOR, μ opioid receptor; LP, lamina propria; ILC3, innate lymphoid cells 3; BBB, blood brain barrier)