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The microbiota\u2013gut\u2013brain 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\n                    <jats:italic>Faecalibacterium<\/jats:italic>\n                    and\n                    <jats:italic>Lactobacillus<\/jats:italic>\n                    , enrichment of proinflammatory phylum Proteobacteria and concurrent dysregulation of microbial metabolites including short\u2010chain fatty acids (SCFAs), tryptophan derivatives and bile acids. These microbial signals mediate bidirectional gut\u2013CNS crosstalk through neuroimmune, neuroendocrine (hypothalamic\u2013pituitary\u2013adrenal (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\u2010related neural circuits. We further elaborate that gut microbiota\u2013driven epigenetic modifications and transgenerational effects reinforce the persistence and heritability of addictive phenotypes. Importantly, microbiota\u2010targeted interventions, including probiotics, prebiotics, faecal microbiota transplantation (FMT) and dietary modulation, can alleviate METH\u2010induced affective disturbances (anxiety\/depression\u2010like behaviours), multiorgan damage (neurotoxicity, reproductive impairment) and relapse risk, via restoring gut microbial homeostasis, repairing intestinal barrier integrity and normalizing gut\u2013brain 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\u2013brain axis\u2013targeted combination therapies for MUD.\n                  <\/jats:p>","DOI":"10.1111\/adb.70171","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T06:18:12Z","timestamp":1788934692000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Research Progress on the Regulatory Mechanisms of Gut Microbiota in Methamphetamine Addiction and Targeted Interventions"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-6168-4268","authenticated-orcid":false,"given":"Jihao","family":"Yang","sequence":"first","affiliation":[{"name":"School of Acupuncture and Tuina Guizhou University of Traditional Chinese Medicine  Guiyang 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