The effect of probiotics on anxiety, depression, nicotine dependence, and metabolic biomarkers in smokers: a randomized clinical trial.

BACKGROUND: Cigarette smoking (CS) has long been associated with both metabolic disturbances and psychological dysfunction. Recent evidence suggests that the gut microbiome may play a role in these processes. This study examined whether probiotic supplementation could influence metabolic markers, nicotine dependence, and symptoms of anxiety and depression in smokers. METHODS: In this randomized, double-blind, placebo-controlled clinical trial, seventy-four adult smokers were recruited (Kashan, Iran) and randomly assigned to receive either probiotic capsules containing Lactobacillus acidophilus, Bifidobacterium longum, Bifidobacterium bifidum, and Bifidobacterium lactis (1.8 × 10⁹ CFU/day; n = 36) or a matching placebo (n = 38) for 12 weeks. Primary endpoints included changes in depressive symptoms (Beck Depression Inventory-II; BDI-II), anxiety (Beck Anxiety Inventory; BAI), and nicotine dependence (Nicotine Dependence Syndrome Scale; NDSS). Secondary endpoints included changes in metabolic, inflammatory, and oxidative stress biomarkers. RESULTS: After 12 weeks, participants receiving probiotics showed significant reductions in fasting plasma glucose, triglycerides, very-low-density lipoprotein (VLDL) cholesterol, and C-reactive protein (CRP) compared with the placebo group (p = 0.025, p = 0.022, p = 0.026, and p = 0.004, respectively). High-density lipoprotein (HDL) cholesterol levels also increased significantly in the probiotic group (p = 0.007). No significant changes were observed in insulin, HOMA-IR, total cholesterol, LDL cholesterol, total antioxidant capacity, plasma nitric oxide, malondialdehyde, glutathione, or in scores for anxiety, depression, and nicotine dependence. CONCLUSIONS: Twelve weeks of probiotic supplementation produced favorable effects on fasting glucose, some lipid profile, and CRP levels in smokers, though no measurable benefits were observed for anxiety and depression symptoms or nicotine dependence. These findings highlight a potential metabolic benefit of probiotics in populations exposed to cigarette smoking. TRIAL REGISTRATION: This trial was registered at the Iranian Registry of Clinical Trials (IRCT20170420033551N13; registration date: December 6, 2022).