Mechanistic Insights into the Link between Gut Dysbiosis and Major Depression: An Extensive Review

Abstract

Depression is a highly common mental disorder, which is often multifactorial with sex, genetic, environmental, and/or psychological causes. Recent advancements in biomedical research have demonstrated a clear correlation between gut dysbiosis (GD) or gut microbial dysbiosis and the development of anxiety or depressive behaviors. The gut microbiome communicates with the brain through the neural, immune, and metabolic pathways, either directly (via vagal nerves) or indirectly (via gut- and microbial-derived metabolites as well as gut hormones and endocrine peptides, including peptide YY, pancreatic polypeptide, neuropeptide Y, cholecystokinin, corticotropin-releasing factor, glucagon-like peptide, oxytocin, and ghrelin). Maintaining healthy gut microbiota (GM) is now being recognized as important for brain health through the use of probiotics, prebiotics, synbiotics, fecal microbial transplantation (FMT), etc. A few approaches exert antidepressant effects via restoring GM and hypothalamus–pituitary–adrenal (HPA) axis functions. In this review, we have summarized the etiopathogenic link between gut dysbiosis and depression with preclinical and clinical evidence. In addition, we have collated information on the recent therapies and supplements, such as probiotics, prebiotics, short-chain fatty acids, and vitamin B12, omega-3 fatty acids, etc., which target the gut–brain axis (GBA) for the effective management of depressive behavior and anxiety.

A Pilot Study of the Gut Microbiota Associated With Depressive Symptoms and Sleep Disturbance Among Chinese and Korean Immigrants in the United States

“…Novel findings pertaining to this study suggest that the MGB axis plays a potential role in the regulation of depressive symptoms and sleep disturbance (Naseribafrouei et al, 2014; Smith et al, 2019). Specifically, the GM affects the central nervous system through various bidirectional biological pathways either directly through anatomical connections (e.g., vagal nerves) or indirectly via microbial-derived metabolites (e.g., SCFAs) and entero-and neuroendocrine peptides (Sonali et al, 2022). The bidirectional nature of the MGB axis has been widely implicated in animal models.…”

Gut microbiota and microbiota-based therapies for Clostridioides difficile infection

“…From a phase 3 randomized, controlled trial, using a the CDiff32, a CDI-specific measure of QoL, patients receiving an LBP reported significant improvements in mental health-related QoL as early as week 1, which continued throughout the 8-week blinded study period ( 75 ). While definitive mechanisms linking changes in the gut microbiota to mental state have not been determined, it is clear that there is a link ( 76 ).…”

Pharmacological, Neurochemical, and Behavioral Mechanisms Underlying the Anxiolytic- and Antidepressant-like Effects of Flavonoid Chrysin

“…Currently, there is growing evidence proposing that dysregulation in the composition of the gut microbiota is related to the pathophysiology of anxiety and depression disorders due to its interaction with neuroimmune, neuroendocrine, and neural pathways [ 66 , 67 ]. These pathways are part of the brain–gut–microbiota axis that may modulate brain development and function, which also impacts on behavior.…”