Epigenetics in depression and gut-brain axis: A molecular crosstalk

Abstract

Gut-brain axis is a dynamic, complex, and bidirectional communication network between the gut and brain. Changes in the microbiota-gut-brain axis are responsible for developing various metabolic, neurodegenerative, and neuropsychiatric disorders. According to clinical and preclinical findings, the gut microbiota is a significant regulator of the gut-brain axis. In addition to interacting with intestinal cells and the enteric nervous system, it has been discovered that microbes in the gut can modify the central nervous system through metabolic and neuroendocrine pathways. The metabolites of the gut microbiome can modulate a number of diseases by inducing epigenetic alteration through DNA methylation, histone modification, and non-coding RNA-associated gene silencing. Short-chain fatty acids, especially butyrate, are well-known histone deacetylases inhibitors. Similarly, other microbial metabolites such as folate, choline, and trimethylamine-N-oxide also regulate epigenetics mechanisms. Furthermore, various studies have revealed the potential role of microbiome dysbiosis and epigenetics in the pathophysiology of depression. Hence, in this review, we have highlighted the role of gut dysbiosis in epigenetic regulation, causal interaction between host epigenetic modification and the gut microbiome in depression and suggest microbiome and epigenome as a possible target for diagnosis, prevention, and treatment of depression.

Gut microbiota dysbiosis in polycystic ovary syndrome: Mechanisms of progression and clinical applications

“…It is a neuroendocrine immune network formed by the central nervous system, the intestinal nervous system, the hypothalamus pituitary adrenal axis and the intestine. The abnormal metabolism of gut microbiota will lead to abnormal secretion of intestinal endopeptides, cytokines and inflammatory factors (Begum et al, 2022). Various gastrointestinal hormones interact with the braingut axis (Yin et al, 2022).…”

A Microbial-Based Approach to Mental Health: The Potential of Probiotics in the Treatment of Depression

“…Nevertheless, the existing studies provide some solid footing for understanding the possible epigenetic basis of probiotics in depression [ 2 , 164 , 173 , 176 , 177 , 178 ]. Epigenetic mechanisms introduce long-lasting, heritable, yet reversible phenotypic changes without involving genotypic alteration through methylation of deoxyribonucleic acid (DNA), histone modification, and non-coding ribonucleic acid (RNA) [ 2 , 175 , 176 , 177 , 178 , 179 , 180 , 181 ]. DNA methylation is predominantly associated with a suppressive effect on gene transcription, whereas histone acetylation is associated with a gene induction effect [ 182 ].…”

“…Environmental factors, including gut microbes and related metabolites, alter the host’s epigenetic signatures, inducing varying responses and favorable or deranged outcomes involving an inflammatory cascade due to the alteration within the gut-brain axis. Gut-modulating agents such as probiotics act as epi-drivers to exert beneficial modulatory epigenetic effects on the host epigenome [ 175 , 181 , 183 , 184 ]. Probiotics exert prophylactic and nullifying epigenetic effects to counter the adverse alteration of the host’s epigenetic signatures [ 164 , 184 ].…”

“…Other studies have demonstrated the epigenetic potential of probiotics through the regulation of BDNF and histone deacetylase (HDAC) inhibition by its metabolites consisting of short-chain fatty acids (SCFAs), mainly butyrate, propionate, and acetate [ 2 , 175 , 181 ]. HDAC inhibition acts at the level of the hippocampus and amygdala and has an activation role on histone acetylation, which is associated with the consolidation of learning and memory [ 186 ].…”

MeCP2 Is an Epigenetic Factor That Links DNA Methylation with Brain Metabolism

“…Such mechanisms include DNA methylation, RNA modification, three-dimensional chromatin structure, chromatin remodeling, nucleosome re-positioning, histone post-translational modifications (PTMs), and the activity of non-coding regulatory RNA molecules, among others [ 5 , 6 , 7 ]. Aberrant epigenetic mechanisms are associated with an extensive variety of human diseases, from different types of cancer, organ malfunction, developmental abnormalities, neurodevelopmental and neurological disorders, and mental disability [ 8 , 9 , 10 , 11 ]. Of note, DNA methylation has been extensively studied regarding normal physiological conditions of human health and disease states.…”