Compound Lactic Acid Bacteria Alleviate Metabolic Dysregulation in Rhesus Macaques with Chronic Restraint Stress Via...

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. In the present study, we apply compound lactic acid bacteria (CLAB) (Lacticaseibacillus rhamnosus GG and Enterococcus faecium) administration therapy to investigate the effect of gut microbiota (GM) on chronic restraint stress (CRS)-depression and its related glucose-lipid metabolism disturbance. We established a non-human primate model of CRS depression to mimic the depressive state in humans and applied CLAB for gastric gavage treatment. CRS macaques exhibit marked depressive-like behavior and disrupted GM structure, decreased levels of C1q/tumor necrosis factor-related protein 9 (CTRP9) and increased levels of CTRP5, and induced insulin resistance (IR) and lipid metabolism disorders. Treatment with CLAB normalized GM structure in CRS macaques, increased the abundance of Lactobacillus murinus and Lactobacillus reuteri, and reduced depressive-like behavior in CRS macaques, with a rebound in CTRP9 and HDL-C levels, reduced CTRP5 and TG levels and improved IR. In addition, CLAB may serve as a promising non-pharmacological intervention that alleviates depression-related metabolic dysregulation by modulating the gut microbiota and improving lipid and glucose metabolism.