In recent years, interest has grown in how diet influences brain function through the gut microbiome , yet the topic is still largely understudied. A recent review article, led by Dr Rajiv R. Ratan from the Brain and Mind Research Institute (BMRI) in New York, explores the provocative idea a high-fibre diet can prevent neurodegeneration in the brain by increasing butyrate in the colon.
Diet-derived substrates impact bacterial community structure and metabolism in the colon. Short-chain fatty acids (SCFAs) formed by microbial fermentation have an important effect on both colonic and systemic host health. Butyrate in particular is primarily synthesized through the fermentation of resistant starch (e.g. tubers) and fructo-oligosaccharides (FOS) (e.g. bananas and asparagus) by bacteria in the colon. Butyrate can also be produced in lower concentrations by mammalian cells and can be found in plant oils and animal fats (e.g. butter is the richest dietary source of butyrate).
Butyrate is a molecule with a wide range of biological functions, which makes it attractive for therapeutic purposes. It has been shown to exert direct effects upon gene expression in mammalian cells through histone deacetylase inhibition, although this effect is not specific to histone proteins alone. It is a potential therapeutic for neurological diseases, as many common neurological diseases show reduced histone acetyltransferase (HAT) activity. Sodium butyrate (NaB) has demonstrated neurotrophic effects in mouse models of Parkinson’s disease, in cisplatin-induced hearing loss, and in cases of disease-associated or toxicity-induced dementia, such as Alzheimer’s disease. These effects result in an improvement of behavioural outcomes, including learning and memory, which can be explained by the up-regulation of genes involved in promoting cell survival, plasticity and regeneration.
Furthermore, butyrate can assist as an energy metabolite to produce adenosine triphosphate (ATP). It serves as a preferred energy source for colonocytes and the researchers of this review hypothesize that if sufficient butyrate levels could be reached in the brain, it could be used as an energy substrate, as in the colon. This would be an important outcome, as energy dyshomeostasis occurs in the brain in many neurological diseases (e.g. in Alzheimer’s, the brain has reduced glucose utilization from the earliest stages of the disease). Aside from its metabolic effects, butyrate might help to rectify the disease-associated mitochondrial dysfunction in the brain secondary to reduced brain glucose availability.
Last, but not least, butyrate can act as a G protein-coupled receptor (GPCR) activator. Some GPCRs have been identified as receptor targets for SCFAs. Strikingly, butyrate induces anti-inflammatory effects through activation of GPR109a, which is a kind of GPCR expressed in colonocytes, T cells, and microglia. It is thought that this receptor could be a good target for therapeutics in Parkinson’s disease.
Available data shows a strong connection between the gut microbiota, butyrate and the brain. According to a study performed in mouse models, either butyrate-producing bacteria or an oral gavage of NaB can restore blood-brain barrier permeability in germ-free mice. Also, mice fed a diet high in fermentable fibre recover faster and show attenuated neuroinflammation after exposure to lipopolysaccharide. Taking these data together, the authors hypothesize that the elevated butyrate from the dietary fibre fermentation may contribute to both the beneficial neurological and immune effects on host health.
Regarding human populations, the beneficial effects of a high-fibre diet on memory and cognition are starting to be explored. Several studies show that probiotics could lower psychological stress in healthy human subjects and in subjects with chronic fatigue syndrome by increasing butyrate-producing bacteria. However, elevated SCFAs in the bloodstream due to increased gut permeation by abnormal microbiota may be unfavorable for children with autism spectrum disorders.
In conclusion, a high-fibre diet is hypothesized to prevent and/or treat brain disorders by elevating butyrate in the gut. More research is needed in order to elucidate the possible pharmacological beneficial effect of butyrate on brain disorders, including neurodegenerative diseases and psychological disorders.
Bourassa MW, Alim I, Bultman SJ, Ratan RR. Butyrate, neuroepigenetics and the gut microbiome: can a high fiber diet improve brain health? Neurosci Lett. 2016; doi:10.1016/j.neulet.2016.02.009.
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