The Role of Lactobacillus helveticus in Mood Regulation: A Narrative Review

Background: Emerging research implicates the microbiota–gut–brain axis (MGBA) in the pathophysiology of depression and anxiety disorders, with Lactobacillus helveticus proposed as a psychobiotic candidate due to its capacity to modulate neurotransmission and stress responses.Methods: Peer reviewed studies (2014–April 2025) were identified via PubMed and clinical trial registries, including rodent stress paradigms, enterochromaffin cell assays, and human randomized controlled trials assessing mood outcomes. Data on behavioral endpoints, neuroendocrine measures, cytokine profiles, gut barrier integrity, and microbial metabolites were extracted.Results: In vitro, L. helveticus WHH1889 upregulated Tph1 expression and elevated 5 HTP synthesis in enterochromaffin cells. In chronic stress (CUMS) and endogenous depression models, strains WHH1889 and NS8 normalized depressive and anxiety like behaviors, restored hippocampal 5 HT/5 HTP pools, attenuated corticosterone hypersecretion, and rebalanced microbial diversity. Clinical trials of heat killed L. helveticus MCC1848 reported significant improvements in positive affect dimensions (e.g., friendliness, relaxation) without adverse events. Systematic reviews confirm overall reductions in depressive symptoms across probiotic interventions but highlight heterogeneity in strains and endpoints.Conclusion: L. helveticus strains demonstrate multifaceted MGBA modulation—enhancing neurotransmitter synthesis, regulating the HPA axis, reducing neuroinflammation, and fortifying gut barrier function—thereby ameliorating mood disturbances. Standardized, large scale, strain specific RCTs in treatment resistant and familial depression populations are warranted to validate clinical efficacy.