Antidepressant Effect of Wild Sidr Honey and Indigenous Probiotics in Unpredictable Chronic Mild Stress (UCMS) Mouse Model

Abstract

Depression is a pervasive and devastating psychiatric disorder. Several fiercely debated theories attempt to explain the pathogenesis of depression; however, the exact etiology remains unclear. Hypotheses of depression relate depression to dysregulation of the HPA axis, genetic predisposition and epigenetic causes, neurotransmitter imbalances, oxidative stress and inflammation, disturbances in the circadian rhythm as well as to metabolic disorders and the gut-brain axis. Over the past few years, the gut-brain axis and the treatment of depression through probiotics, prebiotics, and functional foods has gained attention. A substantial body of research has shown that the gut microbiome and probiotics play a role in mental health and psychiatric disorders. Additionally, the currently available treatments for depression have been associated with delayed onset, severe side effects, and risk of relapse. Therefore, depression can be treated by modulating the gut microbiome using probiotics and functional foods. This study explored the antidepressant effects of wild Sidr honey, Limosilactobacillus fermentum (FM6), and Lacticaseibacillus rhamnosus (FM9 and Y59) in the UCMS mice model of depression. Mice subjected to various stressors of the UCMS protocol were treated with honey and probiotics, both individually and in combination, the results were compared to those of fluoxetine. Behavioral tests and histological analyses of the mice samples were conducted, and the results were analyzed. The results showed significant improvements in behavioral tests, improving depressive like behavior, anhedonia, and despair. Furthermore, histological analysis showed improvements and restoration in the hippocampal structure and cell count, as well as in the structure of the colon. The findings suggest that probiotics and honey can provide an alternative treatment to depression while causing minimal or no significant side effects.