Perturbations in the Gut Microbiome of C57BL/6J Mice by the Sobriety Aid Antabuse® (Disulfiram)

J Appl Microbiol. 2024 Dec 19:lxae305. doi: 10.1093/jambio/lxae305. Online ahead of print.

Abstract

Aims: Disulfiram (Antabuse®) is an oral alcohol sobriety medication that exhibits antimicrobial activity against Gram-positive facultative anaerobes. The aims of this study were to measure the antimicrobial activity against anaerobic bacteria of the gut human microbiome and establish the extent that disulfiram alters the microbial composition of the ileum, cecum, and feces using C57BL/6 mice.

Methods and results: Antimicrobial susceptibility testing by the microdilution method revealed that disulfiram inhibits the in vitro growth of gut anaerobic species of Bacteroides, Clostridium, Peptostreptococcus, and Porphyromonas. Differential sequencing of 16S rRNA isolated from the ileum, cecum, and feces contents of treated vs. untreated mice showed disulfiram enriches the Gram-negative enteric population. In female mice, the enrichment was greatest in the ileum whereas the feces composition in male mice was the most heavily altered.

Conclusions: Daily administration of oral disulfiram depletes the enteric Gram-positive anaerobe population as predicted by the MIC data for isolates from the human gut microbiota.

Keywords: anaerobes; antimicrobials; intestinal microbiology; microbiome; pharmaceuticals.