The role of the gut–brain axis in the pathogenesis of depression and anxiety disorders: The significance of microbiota, bacterial metabolites, and vagus nerve signalling — A systematic review

Abstract

Introduction and aim: Depression and anxiety disorders are leading causes of disability worldwide, and many patients respond inadequately to conventional treatment. The microbiota–gut–brain axis has emerged as a candidate contributor to their pathogenesis. This review aimed to synthesise mechanistic and clinical evidence linking gut microbiota, bacterial metabolites, and vagal signalling to depression and anxiety. Material and methods: A systematic search of PubMed, Embase, and Scopus (2011–2025) was performed following PRISMA principles, using terms for the gut–brain axis, microbiota, short-chain fatty acids, tryptophan, vagus nerve, depression, and anxiety. Studies were synthesised narratively across three mechanistic pillars. Results: Patients with depression and anxiety show reduced short-chain-fatty-acid-producing taxa and enrichment of pro-inflammatory bacteria. Bacterial metabolites—short-chain fatty acids, tryptophan catabolites, and gamma-aminobutyric acid—modulate neuroinflammation, blood–brain-barrier integrity, and neurotransmission. Several anxiolytic and antidepressant-like microbial effects are abolished by vagotomy, confirming a vagal route. Randomised trials of psychobiotics show small but significant reductions in depressive symptoms. Conclusions: The gut–brain axis is a biologically plausible, therapeutically tractable contributor to mood and anxiety disorders, though heterogeneity and causal uncertainty remain.