Oleoylethanolamide supplementation enriches Akkermansia muciniphila and modulates intestinal barrier function in adults with obesity: A randomized, double-blind, placebo-controlled trial

Targeted modulation of the gut microbiome represents a promising nutritional strategy to support metabolic and intestinal health in overweight and obese adults. Oleoylethanolamide (OEA) is an endogenous lipid mediator that regulates satiety, lipid metabolism, and inflammation, but its effects on the human microbiome are not well defined. In this randomized, double-blind, placebo-controlled trial, 57 adults with obesity (BMI 30–40 kg/m²) received either 300 mg of TRPTI, providing 250 mg/day of OEA (n = 28), or placebo (n = 29) for 12 weeks. Outcomes included shotgun metagenomics, microbiome profiling, intestinal barrier and inflammatory biomarkers, and safety measures. OEA was safe and well-tolerated with no adverse changes in clinical biomarkers. Although overall microbial diversity remained stable, OEA induced selective, health-relevant compositional shifts. Notably, Faecalibacterium prausnitzii and Akkermansia muciniphila were enriched. These changes coincided with functional host benefits, including increased occludin at Week 12 and interleukin-2 at Week 6, while reducing interleukin-1β, consistent with improved epithelial barrier dynamics and reduced inflammation. Functional pathway analysis suggested enhanced microbial metabolic and redox capacity. These findings indicate OEA supplementation selectively enriches beneficial gut bacteria – particularly A. muciniphila, while improving gut barrier biomarkers and immune function without disrupting microbiome stability. These findings position OEA as a safe, targeted microbiome-modulating ingredient with potential applications for supporting gut and metabolic health.