GLP-1 Diabetes Drug Triggers Mood-Boosting Gut Bacteria and Endocannabinoid Pathway
In mice, the GLP-1 drug liraglutide reduces depressive-like behavior not by acting in the brain, but by accumulating in the gut where it promotes Lactobacillus delbrueckii. This bacterium increases levels of the endocannabinoid 2-AG via diacylglycerol, dampening stress-related brain activity. The antidepressant effect disappears if the gut microbiota is depleted, indicating a microbiome-dependent, brain-receptor–independent mechanism. The findings suggest potential for targeted probiotics to treat depression in obesity/diabetes, though human trials and sex-inclusive studies are needed.