Potential Contribution of the Intestinal Microbiome to Phenethylamine-Induced Hyperthermia

Phenethylamines (e.g., methamphetamine) are a common source of drug toxicity. Phenethylamine-induced hyperthermia (PIH) can activate a cascade of events that may result in rhabdomyolysis, coagulopathy, and even death. Here, we review recent evidence that suggests a potential link between the gut-brain axis and PIH. Within the preoptic area of the hypothalamus, phenethylamines lead to changes in catecholamine levels, that activate the sympathetic nervous system (SNS) and increase the peripheral levels of norepinephrine (NE), resulting in: (1) the loss of heat dissipation through α1 adrenergic receptor ( α1-AR)-mediated vasoconstriction, (2) heat generation through β-AR activation and subsequent free fatty acid (FFA) activation of uncoupling proteins (UCPs) in brown and white adipose tissue, and (3) alteration of the gut microbiome and its link to the gut-brain axis. Recent studies have shown that phenethylamine derivatives can influence the composition of th e gut microbiome and thus its metabolic potential. Phenethylamines increase the relative level ofProteuswhich has been linked to enhanced NE turnover. Bidirectional fecal microbial transplants (FMT) between PIH-tolerant and PIH-na ïve rats demonstrated that the transplantation of gut microbiome can confer phenotypic hyperthermic and tolerant responses to phenethylamines. These phenethylamine-mediated changes in the gut microbiome were also associated with epigenetic changes in the mediators of thermogenesis. Given the ...
Source: Brain, Behavior and Evolution - Category: Neurology Source Type: research