Exploring the Gut and Oral Microbiomes in Psychoactive Substance Use: A Scoping Review of Clinical Studies.

Substance use disorders (SUDs) constitute a significant global health challenge, and emerging evidence suggests that the gut and oral microbiomes may play significant roles in addiction pathophysiology, yet the human clinical literature remains fragmented. This scoping review systematically synthesizes evidence from 75 clinical studies investigating alterations in gut and oral microbiomes associated with alcohol, stimulant, cannabis, and opioid use. Across studies, beta-diversity analyses frequently reveal clear differences between substance users and controls, indicating distinct community structures. Findings on alpha diversity and specific taxonomic shifts vary by substance. Commonly observed changes included declines in beneficial short-chain fatty acid-producing taxa, alongside expansions of opportunistic or proinflammatory microorganisms. However, substantial methodological heterogeneity, including variations in study design, population characteristics, and analytical methods, complicates direct comparisons and definitive conclusions. Limited longitudinal evidence indicates partial microbiome recovery after extended abstinence, although full restoration remains uncertain. Further longitudinal research with standardized methods is needed to clarify these findings and inform potential microbiome-targeted therapies for SUDs.