Microbial genes, brain & behaviour – epigenetic regulation of the gut–brain axis

Abstract

To date, there is rapidly increasing evidence for host-microbe interaction at virtually all levels of complexity, ranging from direct cell-to-cell communication to extensive systemic signalling, and involving various organs and organ systems, including the central nervous system. As such, the discovery that differential microbial composition is associated with alterations in behaviour and cognition has significantly contributed to establishing the microbiota-gut-brain axis as an extension of the well-accepted gut-brain axis concept. Many efforts have been focused on delineating a role for this axis in health and disease, ranging from stress-related disorders such as depression, anxiety and irritable bowel syndrome to neurodevelopmental disorders such as autism. There is also a growing appreciation of the role of epigenetic mechanisms in shaping brain and behaviour. However, the role of epigenetics in informing host-microbe interactions has received little attention to date. This is despite the fact that there are many plausible routes of interaction between epigenetic mechanisms and the host-microbiota dialogue. From this new perspective we put forward novel, yet testable, hypotheses. Firstly, we suggest that gut-microbial products can affect chromatin plasticity within their host's brain that in turn leads to changes in neuronal transcription and eventually alters host behaviour. Secondly, we argue that the microbiota is an important mediator of gene-environment interactions. Finally, we reason that the microbiota itself may be viewed as an epigenetic entity. In conclusion, the fields of (neuro)epigenetics and microbiology are converging at many levels and more interdisciplinary studies are necessary to unravel the full range of this interaction.

Physical activity level is impaired and diet dependent in preterm newborn pigs

“…Related to emotional behavior, the neurotransmitter serotonin has been suggested as a central link between the gut and brain (37). Serotonin located in and secreted from the enteric nervous system regulates many aspects of intestinal function, including GIT immunity and motility (13), and the expression of GIT serotonergic cells is developmentally regulated, also in pigs (38). In our preliminary studies on the volume of intestinal serotonergic cells in experiment 2, we found an increase from middle to distal gradient in the volume density, and enteral nutrition with BC tended to increase the volume density of serotonergic cells distally, relative to IF and TPN.…”

“…In addition to the direct effects of nutrients and dietary factors on neurodevelopmental endpoints, indirect effects may arise from links between the early diet on gut growth, enteric nervous system, signaling molecules like serotonin (5-HT), and/ or gut microbiota. Studies in mice show that changes in the gut microbiota after birth, in parallel with the first enteral feeding, lead to an anxiety-depression-like behavior (13) and other behavioral changes (14). Whether such effects are mediated by changes in gut physiology and microbiology, resulting in metabolic, endocrine, or neuronal effects on the brain and central nervous system (CNS), are unknown.…”

Gastroenterology issues in schizophrenia: Why the gut matters

“…In rodent models, we learned that experimental manipulations of gut microbiota induce behavioral, biochemical and molecular sequelae, with stunning reversals in phenotype using germ-free animals, vagectomy, probiotics and antibiotics [116,117,67,[118][119][120]. In a new report from our laboratory, we found in microbiome analyses of the oral pharynx of people with schizophrenia that there were significantly differential levels of a bacterial phage, Lactobacillus phiadh, and that these levels correlated with the presence of immunological conditions.…”

Microbes, Immunity, and Behavior: Psychoneuroimmunology Meets the Microbiome

“…GF mice have an altered expression of genes involved in neuropeptide production (El Aidy et al, 2013) together with genes involved in brain development and behavior (Diaz Heijtz et al, 2011;Stilling et al, 2014). GF mice have significant neurochemical alterations, which are reflected in markedly altered behavior patterns including stress responses.…”

“…SCFAs are a major source of energy for colonic epithelial cells, are involved in the prevention of DNA and cell damage, can stimulate sodium absorption, and impact immune and inflammatory responses, while sodium butyrate has been shown to elicit an antidepressant effect in mice (Schroeder et al, 2007). It has been postulated that SCFAs can help prevent colorectal cancer and they have been reported to alter gene expression of cell cycle regulators, in vitro (Scheppach et al, 1995;Siavoshian et al, 1997;Stilling et al, 2014). As well as playing a role as epigenetic regulators by HDAC inhibition, SCFAs bind to G-protein coupled receptors (GPCRs) (Maslowski et al, 2009).…”