Addiction biologySep 9, 2026

How Gut Bacteria May Influence Methamphetamine Addiction and Possible Treatments

Gut-Brain Axis Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Sep 10, 2026

Abstract

Methamphetamine exposure induces significant gut microbiota dysbiosis, including the loss of beneficial bacteria.

METH exposure leads to a reduction of beneficial gut bacteria such as Faecalibacterium and Lactobacillus.
An increase in proinflammatory bacteria from the Proteobacteria phylum is observed following METH exposure.
Dysregulated microbial metabolites, including short-chain fatty acids and tryptophan derivatives, are associated with METH addiction.
Gut microbiota signals may influence brain function through neuroimmune and neuroendocrine pathways, impacting addiction-related brain circuits.
Microbiota-targeted interventions have potential to alleviate METH-related issues like anxiety, neurotoxicity, and the risk of relapse.

Simplified

Methamphetamine (METH) is a globally prevalent, highly addictive synthetic psychostimulant, for which no FDA-approved pharmacotherapy is currently available for METH use disorder (MUD). The microbiota-gut-brain axis has been well established as a key regulatory pathway in substance use disorders, yet its specific mechanistic basis and translational potential in METH addiction remain to be systematically elucidated. This review synthesizes current preclinical and clinical evidence demonstrating that METH exposure induces profound gut microbiota dysbiosis, characterized by the depletion of beneficial genera such as Faecalibacterium and Lactobacillus, enrichment of proinflammatory phylum Proteobacteria and concurrent dysregulation of microbial metabolites including short-chain fatty acids (SCFAs), tryptophan derivatives and bile acids. These microbial signals mediate bidirectional gut-CNS crosstalk through neuroimmune, neuroendocrine (hypothalamic-pituitary-adrenal (HPA) axis) and vagal pathways, thereby exacerbating the core central pathologies of METH addiction: neurotransmitter system imbalance, neuroinflammation and oxidative stress and dysfunction of addiction-related neural circuits. We further elaborate that gut microbiota-driven epigenetic modifications and transgenerational effects reinforce the persistence and heritability of addictive phenotypes. Importantly, microbiota-targeted interventions, including probiotics, prebiotics, faecal microbiota transplantation (FMT) and dietary modulation, can alleviate METH-induced affective disturbances (anxiety/depression-like behaviours), multiorgan damage (neurotoxicity, reproductive impairment) and relapse risk, via restoring gut microbial homeostasis, repairing intestinal barrier integrity and normalizing gut-brain axis signalling. Collectively, this review positions the gut microbiota as a critical peripheral regulatory node in METH addiction, providing a robust preclinical foundation for the development of gut-brain axis-targeted combination therapies for MUD.