Gut Homeostasis, Microbial Dysbiosis, and Opioids

Abstract

Gut homeostasis plays an important role in maintaining animal and human health. The disruption of gut homeostasis has been shown to be associated with multiple diseases. The mutually beneficial relationship between the gut microbiota and the host has been demonstrated to maintain homeostasis of the mucosal immunity and preserve the integrity of the gut epithelial barrier. Currently, rapid progress in the understanding of the host-microbial interaction has redefined toxicological pathology of opioids and their pharmacokinetics. However, it is unclear how opioids modulate the gut microbiome and metabolome. Our study, showing opioid modulation of gut homeostasis in mice, suggests that medical interventions to ameliorate the consequences of drug use/abuse will provide potential therapeutic and diagnostic strategies for opioid-modulated intestinal infections. The study of morphine's modulation of the gut microbiome and metabolome will shed light on the toxicological pathology of opioids and its role in the susceptibility to infectious diseases.

Keywords: dysbiosis; gut microbiota; homeostasis; opioid-related disorders.

Figure 1.

Illustration of gut homeostasis and dysbiosis. Gut homeostasis is maintained by commensal bacteria, functional barrier and tolerant immune response. The symbiotic relationship between commensal microbiota and the host achieve a balanced, mutually beneficial state. Alteration in gut microbiome has been shown to contribute to dysregulated immune response, bowel dysfunction and gut barrier disruption.

Figure 2.

Model of metabolism and biotransformation of morphine and bile acids. In liver, cholesterol were transformed to primary bile acids, and morphine were conjugated to M3G. In gut, intestinal bacteria transform primary bile acids and M3G into secondary bile acids and morphine respectively. Bile acids and morphine are reabsorbed and recycled via enterohepatic circulation. MS: Morphine sulfate; M3G: Morphine-3-glucuronide.