The Relationship Between Epigenetics and Microbiota in Neuropsychiatric Diseases

Abstract

Microbiota might be considered as a pool for environmental epigenetic factors. Evidence is accumulating that environmental exposures – including microbes, diet, drugs – play a role in the pathogenesis of many neuropsychiatric disorders. Underlying mechanisms are complex, involving the sensitive interplay of genetics with epigenetics, neuroinflammation and the innate immune system. Modifications of microbiota affect neurogenesis and the maturation of microglia, influencing social behavior, stress-related responses and fear learning mechanisms. The excitatory neurons in the medial prefrontal cortex appear to play a key role. The mechanisms through which antibiotics administration may modulate microbiota and, therefore, behavior and neuropsychiatric disorders, may be influenced by several variables such as pre-existing gastrointestinal inflammation, the baseline microbiota composition, diet and stress perception. Probiotics, individualized diet, antibiotics and fecal transplantation could positively modulate the effects of epigenetic factors on neuropsychiatric disorders.

Strategic Modification of Gut Microbiota through Oral Bacteriotherapy Influences Hypoxia Inducible Factor-1α: Therapeutic Implication in Alzheimer’s Disease

“…Potentially negative side effects of microbiome alterations [ 29 ] should be carefully evaluated [ 4 ] in future pre-clinical and clinical studies. In fact, microbiome structure and genetic and epigenetic factors can influence the final effect [ 30 ]. SLAB51 beneficially impacts gut microbiota in 3xTg-AD mice with multi-level mechanisms, and these data contribute to describe another molecular mechanism through which this specific probiotic formulation can counteract oxidation and inflammation and can improve energy metabolism in AD.…”

The Association between Early-Life Gut Microbiota and Long-Term Health and Diseases

“…This happens because early adverse/stressful events can produce long-term epigenetic changes that affect the HPA axis as well as neurotransmitter and neuroendocrine signaling, which may then impair adult cognitive and behavioral functioning [156]. Moreover, altered levels of microbiome-produced metabolites may induce modifications of key disease-susceptible gene expression during critical periods of neurodevelopmental disorders [167].…”

Does the imbalance in the apolipoprotein E isoforms underlie the pathophysiological process of sporadic Alzheimer's disease?

“…ApoE isoforms associated with the neuroinflammatory state of the brain through microglia 32 and epigenomic features related to microglia, are associated with attenuated effect of APOE ε4 on AD risk, including microbiota composition. 33,34 APOE variation, in fact, influences the microbiota composition and its subsequent metabolism.…”