{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T22:45:11Z","timestamp":1791499511474,"version":"4.3.4"},"reference-count":70,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004961","name":"Tecnol\u00f3gico de Monterrey","doi-asserted-by":"publisher","award":["IJST070-23EG71001"],"award-info":[{"award-number":["IJST070-23EG71001"]}],"id":[{"id":"10.13039\/501100004961","id-type":"DOI","asserted-by":"publisher"}]},{"award":["IJST070-23EG71001"],"award-info":[{"award-number":["IJST070-23EG71001"]}],"id":[{"id":"https:\/\/ror.org\/03ayjn504","id-type":"ROR","asserted-by":"publisher"}]},{"name":"SICyT","award":["11834-205"],"award-info":[{"award-number":["11834-205"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Background: Growing evidence suggests that chronic substance use disrupts the gut microbiota composition and function, which can contribute to intestinal dysfunction, systemic inflammation, and gut\u2013brain axis dysregulation. However, current evidence remains fragmented and heterogenous, with most studies focusing on individual substances rather than substance-specific microbial signatures. Objective: Therefore, this systematic review synthesizes recent evidence (2019\u20132025) to characterize the impact of chronic substance use, including alcohol, nicotine, opioids, cocaine, and methamphetamine, on the gut microbiota composition and functional integrity. Methods: Following the PRISMA 2020 guidelines, a total of 91,421 records were identified before screening through searches conducted across electronic databases and publisher platforms, including PubMed, Web of Science, ProQuest, and BSCOhost, among others. After duplication removal and application of the predefined eligibility criteria, 60 studies were selected for qualitative analysis. Results: The findings revealed an interspecies similarity in which chronic substance exposure generally induced dysbiosis characterized by a depletion of beneficial short-chain fatty acid (SCFA)-producing taxa, such as Lactobacillus, Akkermansia, and Faecalibacterium, alongside the enrichment of opportunistic pathogens such as Escherichia-Shigella. Alcohol emerged as a particularly potent ecological driver, consistently reducing the richness and diversity of the microbial community. Mechanistically, these alterations are linked to impaired intestinal barrier function, increased lipopolysaccharide translocation, and the activation of systemic inflammatory pathways. Furthermore, substance-specific metabolic fingerprints were identified, including disruptions in glutamate pathways for cocaine and trimethylamine N-oxide precursors for methamphetamine. Preclinical evidence from fecal microbiota transplantation and germ-free models suggests that these microbial shifts actively modulate reward sensitivity and neuroplasticity through the gut\u2013brain axis. Conclusion: Collectively, the data presented in this study support a shift from reductionist addiction models toward a systems-level framework, positioning the gut microbiome as a pivotal, modifiable component of addiction biology and a promising target for novel therapeutic interventions.<\/jats:p>","DOI":"10.3390\/medsci14030367","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T11:48:32Z","timestamp":1782992912000},"page":"367","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Gut Microbiota in Addiction Biology: A Systematic Review of Substance-Induced Dysbiosis and Gut\u2013Brain Axis Alterations"],"prefix":"10.3390","volume":"14","author":[{"given":"Juan","family":"Esparza-S\u00e1nchez","sequence":"first","affiliation":[{"name":"Escuela de Ingenier\u00eda y Ciencias, Tecnol\u00f3gico de Monterrey, Av. General Ram\u00f3n Corona 2514, Zapopan 45138, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego Alejandro","family":"Garibi-Miranda","sequence":"additional","affiliation":[{"name":"Escuela de Ingenier\u00eda y Ciencias, Tecnol\u00f3gico de Monterrey, Av. General Ram\u00f3n Corona 2514, Zapopan 45138, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Ch\u00e1vez-Tinoco","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica del Desarrollo y Fisiolog\u00eda Molecular, Instituto de Biotecnolog\u00eda (IBT), Universidad Nacional Aut\u00f3noma de M\u00e9xico (UNAM), Cuernavaca 62210, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8252-5211","authenticated-orcid":false,"given":"Jorge L.","family":"Mej\u00eda-M\u00e9ndez","sequence":"additional","affiliation":[{"name":"Escuela de Ingenier\u00eda y Ciencias, Tecnol\u00f3gico de Monterrey, Epigmenio Gonz\u00e1lez 500, San Pablo, Santiago de Quer\u00e9taro 76130, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8023-5533","authenticated-orcid":false,"given":"Maricruz","family":"Sepulveda-Villegas","sequence":"additional","affiliation":[{"name":"Escuela de Ingenier\u00eda y Ciencias, Tecnol\u00f3gico de Monterrey, Av. 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