Chronic opioid use modulates human enteric microbiota and intestinal barrier integrity

Area of Science:

• Microbiology
• Gastroenterology
• Pharmacology

Background:

• Opioid epidemic in the US has led to widespread opioid-induced bowel dysfunction.
• Methadone maintenance treatment (MMT) is a common therapy for opioid use disorder.
• The impact of MMT on the gut microbiome and intestinal barrier remains incompletely understood.

Purpose of the Study:

• To investigate the effects of MMT on the gut microbiome composition.
• To analyze the gut bacterial metabolite profile in MMT patients.
• To assess the impact of MMT on intestinal barrier integrity.

Main Methods:

• Analysis of gut microbiome composition and function.
• Metabolomic profiling of fecal samples.
• In vitro assessment of bacterial metabolite effects on intestinal barrier models.

Main Results:

• Identified dysbiosis characterized by an imbalance in bacteria crucial for SCFA production and barrier integrity.
• Observed reduced levels of fecal SCFAs in MMT patients.
• Demonstrated that Akkermansia muciniphila metabolites enhance intestinal barrier function by modulating pore pathways and tight junctions.

Conclusions:

• MMT induces significant alterations in the gut microbiome and SCFA production.
• Akkermansia muciniphila metabolites hold therapeutic potential for restoring gut barrier integrity.
• Targeting the gut microbiome may offer novel clinical strategies for managing opioid-induced bowel dysfunction.