The effect of minocycline on the gut microbiome in individuals with alcohol use disorder and healthy controls

Alcohol Use Disorder (AUD) has been linked to changes in gut microbial composition. However, many previous microbiome studies have included AUD populations who also had conditions like alcohol-associated liver disease, which made it difficult to determine the specific effects of AUD on gut dysbiosis. Additionally, preclinical research has shown that gut microbiome composition can influence behaviors related to minocycline, such as alcohol-related and emotional behaviors. Nonetheless, there have been no studies examining these effects in humans with AUD.

This study aimed to address these gaps by comparing gut microbiome features between healthy controls (HCs) and individuals with AUD (without alcohol-associated liver disease), and by investigating the impact of minocycline on the human gut microbiome. The study involved a four-week randomized, double-blind, placebo-controlled trial, with 31 individuals with AUD and 26 healthy controls participating.

Fecal samples were collected at the beginning of the study and then weekly for 16S rRNA gene sequencing over the course of the trial.

The results showed that alpha diversity (a measure of the richness and balance of bacterial species within a sample) did not differ between the two groups, whether they were receiving the active medication or a placebo. However, beta diversity (a measure of differences in bacterial composition between samples) did differ between the AUD and control groups, and this difference shifted over time in response to minocycline treatment.

AUD participants were found to have different levels of several bacterial taxa compared to controls. Specifically, they had lower levels of Dialister and Subdoligranulum, and higher levels of Collinsella, Streptococcus, and Phascolarctobacterium. When AUD participants received minocycline, their gut microbiome underwent rapid and significant restructuring, altering the levels of a wide range of bacterial species and metabolic pathways (such as those involved in ubiquinol biosynthesis and methylphosphonate degradation).

Importantly, these changes were seen regardless of whether the individuals had AUD or not - minocycline appeared to produce a similar gut microbiome restructuring in both groups.