Compound lactic acid bacteria alleviate metabolic disorders in rhesus macaques with chronic restraint stress via remodeling the gut microbiota

Chronic stress is a critical risk factor for depression, and prolonged exposure to stressors increases the risk of metabolic dysregulation. Gut microbiota (GM) intervention is a promising therapeutic target for stress-related emotional and behavioral disorders. This study investigates the effects of compound lactic acid bacteria (CLAB) (Lacticaseibacillus rhamnosus GG and Enterococcus faecium) transplantation on chronic restraint stress (CRS)-induced depression and associated metabolic disturbances in rhesus macaques. CRS macaques exhibited depressive-like behavior, altered GM composition, insulin resistance (IR), and lipid metabolism abnormalities. Treatment with CLAB normalized GM structure, increased Lactobacillus murinus and Lactobacillus reuteri abundance, and alleviated depressive-like behavior. It also increased C1q/tumor necrosis factor-related protein 9 (CTRP9) and HDL-C levels, decreased CTRP5 and triglyceride (TG) levels, and improved IR. Our evidence suggests that CRS-induced depression and metabolic disturbances are related to GM disruption, and that lactic acid bacteria may provide a non-pharmacological treatment to restore metabolic homeostasis in stress-related disorders.