Chronic inflammatory diseases are increasingly recognized as the result of disrupted coordination among microbial ecology, epithelial barriers, lipid signaling, and the immune system. While the microbiome-endocannabinoidome (eCBome) axis is known to regulate metabolism and inflammatory tone, distinguishing direct causal crosstalk from mere association remains a major challenge in biomedical research.

Key Highlights from the Review: -The "Immunometabolic Rheostat": The axis was operationalized across five measurable domains: microbial functions/metabolites, compartment-specific eCBome ligands and enzymes, barrier integrity and microbial translocation, immune-cell programming, and tissue/clinical outcomes.

- Beyond Classical Endocannabinoids: The review emphasizes the critical, distinct roles of endocannabinoid-related N-acylethanolamines (like PEA and OEA), which act prominently through PPAR, TRPV1, and GPR119 to regulate inflammation, satiety, and barrier repair.

-Engineered Probiotics as Proof-of-Concept: The review highlight cutting-edge evidence where engineered Lactobacillus paracasei platforms produce PEA or OEA in situ. This provides a direct causal link between defined microbial perturbations, lipid-mediator release, and improved metabolic or inflammatory outcomes, particularly in obesity-associated inflammation and Inflammatory Bowel Disease (IBD).

Summary as published by the college when announcing this work. See the journal article for the full abstract.