Abstract

Substance use disorders (SUDs) and drug-related deaths represent a growing global burden. Increasing evidence highlights substances ability to reshape the gut microbiome, a highly dynamic and metabolically active ecosystem that contributes to host homeostasis through interactions with neural, endocrine, and immune systems.

Alterations in microbial diversity, depletion of short-chain fatty acid–producing taxa, disruption of epithelial barrier integrity, and systemic inflammation have been consistently associated with substance exposure. While these changes are increasingly characterized in living individuals, their persistence and impact after death remain less explored. In forensic contexts, drug-related fatalities are difficult to interpret due to non-specific autopsy findings, analytical limitations of toxicological methods, post-mortem redistribution, and the absence of clear lethal thresholds. The emerging study of thanatomicrobiome offers a novel avenue to address these challenges, as antemortem dysbiosis may influence post-mortem microbial succession and, consequently, post-mortem interval (PMI) estimation.

This narrative review synthesises current knowledge on substance-induced microbiome alterations across antemortem and postmortem contexts, and extends this perspective to entomotoxicology, highlighting how drug-related microbial changes may influence both insect colonisation and insect-associated microbiomes. It also emphasises current methodological heterogeneity and the need for standardised approaches, outlining opportunities for future forensic applications.