Microbiota-Induced Epigenetic Alterations in Depressive Disorders Are Targets for Nutritional and Probiotic Therapies

Abstract

Major depressive disorder (MDD) is a complex disorder and a leading cause of disability in 280 million people worldwide. Many environmental factors, such as microbes, drugs, and diet, are involved in the pathogenesis of depressive disorders. However, the underlying mechanisms of depression are complex and include the interaction of genetics with epigenetics and the host immune system. Modifications of the gut microbiome and its metabolites influence stress-related responses and social behavior in patients with depressive disorders by modulating the maturation of immune cells and neurogenesis in the brain mediated by epigenetic modifications. Here, we discuss the potential roles of a leaky gut in the development of depressive disorders via changes in gut microbiota-derived metabolites with epigenetic effects. Next, we will deliberate how altering the gut microbiome composition contributes to the development of depressive disorders via epigenetic alterations. In particular, we focus on how microbiota-derived metabolites such as butyrate as an epigenetic modifier, probiotics, maternal diet, polyphenols, drugs (e.g., antipsychotics, antidepressants, and antibiotics), and fecal microbiota transplantation could positively alleviate depressive-like behaviors by modulating the epigenetic landscape. Finally, we will discuss challenges associated with recent therapeutic approaches for depressive disorders via microbiome-related epigenetic shifts, as well as opportunities to tackle such problems.

Epigenome Defines Aberrant Brain Laterality in Major Mental Illnesses

“…Nonetheless, they are influenced by diverse environmental factors such as malnutrition, infections, chemical contaminations, ecological conditions, and likely the social environment, as reviewed elsewhere [ 99 , 100 , 101 , 106 , 107 ]. For instance, a deficiency in methionine, choline, folic acid, and vitamin B12, which are essential for the functioning of the methylation machinery, as well as inflammation and oxidative stress induced by a pathological gut microbiome, can lead to epigenetic changes and the loss of epigenetic memory [ 99 , 100 , 101 , 108 , 109 , 110 ].…”

Role of Glial Cells in Depression and Drug Addiction

“…For instance, butyrate, a short-chain fatty acid (SCFA) metabolite of the GM, is critical in maintaining proper gastrointestinal and GBA integrity. Disruption of its function can lead to MDD [219] [220]. Conversely, sodium butyrate, can exert antidepressant effects.…”

Role of Glial Cells in Neuronal Function, Mood Disorders, and Drug Addiction

“…For instance, butyrate, a SCFA metabolite of the GM, is critical in maintaining proper gastrointestinal and GBA integrity. Disruption of its function can lead to MDD [ 257 , 258 ]. Conversely, sodium butyrate can exert antidepressant effects.…”