Probiotics as Modulators of Adult Neurogenesis and Synaptic Plasticity: New Perspectives in the Pathophysiology and Treatment of Affective Disorders

Affective disorders, such as major depressive disorder and anxiety disorders, represent a major global health burden, with current treatments proving inadequate for a substantial proportion of patients. Emerging research highlights the microbiota-gut-brain (MGB) axis as a crucial bidirectional communication system influencing brain function and neuroplasticity through neural, endocrine, immune, and metabolic pathways. This narrative review examines probiotics-live beneficial microorganisms-as modulators of adult neurogenesis and synaptic plasticity, two processes fundamentally implicated in the pathophysiology of affective disorders. Preclinical evidence demonstrates that specific strains, particularly from the Lactobacillus and Bifidobacterium genera, promote hippocampal neurogenesis and synaptic function through epigenetic regulation via short-chain fatty acids (SCFAs), notably butyrate-mediated histone deacetylase inhibition, modulation of neuroinflammatory pathways, regulation of neurotransmitter receptor expression across glutamatergic, GABAergic, and monoaminergic systems, and production of neuroactive peptides. Clinical evidence from randomized controlled trials and recent meta-analyses indicates that probiotic supplementation produces significant reductions in depressive and anxiety symptoms, with effects correlating to changes in gut microbiota composition and peripheral neuroplasticity biomarkers, particularly brain-derived neurotrophic factor (BDNF). However, significant methodological limitations persist, including small sample sizes, lack of standardization in probiotic strains and dosages, inconsistent outcome measures, and considerable interindividual variability. While the mechanistic and clinical evidence is biologically plausible and directionally promising, it is not yet sufficient to support definitive therapeutic recommendations. Future research must prioritize adequately powered clinical trials with standardized consortia, comprehensive multi-omics biomarker panels, and precision psychobiotic strategies guided by microbiome-defined patient stratification.