action that influence the gut-brain axis. Notably, they proposed that the butyrate produced through fermentation of dietary fiber boosts the health of mitochondria located in the brain.
"While the metabolic events in the colon may appear disconnected from that of the brain, it's important to consider the immense energy demands of the brain and the energy dyshomeostasis that occurs in the brain in many neurological diseases.
Perhaps the best cited example is the reduced glucose utilization in the Alzheimer's brain, which occurs at the earliest stages of the disease and well before memory loss …
However, we hypothesize that if sufficient butyrate levels could be reached in the brain, butyrate could stand in as an energy substrate, as in the colon, and restore energy homeostasis," the researchers said.4
• The dangers of reduced glucose availability in the brain — The study authors highlighted this problem, which "is believed to contribute to mitochondrial dysfunction in acute and chronic neurological diseases."5 These findings reinforce what I've written about before, which is the health dangers of following a low-carb diet, as your body actually needs carbs to function at an optimal state.
• Butyrate lowers the risk of colon cancer — Based on the evidence reviewed by the researchers, butyrate activates GPR109a (a G protein-coupled receptor found on the surface of cells), which belongs to the larger family of G protein-coupled receptors (GPCRs).
This receptor is present in colonocytes (cells lining the colon) and T cells (immune cells), and when this particular protein is expressed, it triggers programmed cell death (apoptosis) in human colon cancer cells.
A Deeper Dive Into Butyrate's Ability to Inhibit Neuroinflammation
Butyrate also inhibits proinflammatory signaling pathways, such as the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway, a master regulator of inflammation. As explained in the Neuroscience Letter paper:6
"Treatment with β-hydroxybutyrate induced anti-inflammatory effects in both in vitro and in vivo models of Parkinson's disease through GPR109a activation and down regulating NF-κB activation. The neurons were also protected from LPS- induced [editor's note: endotoxin-induced] injury and improved behavioral outcomes in the animal models."
By inhibiting NF-κB activation, butyrate curtails the production of inflammatory mediators like cytokines,7 which promote synaptic dysfunction that contributes to worsening brain health.8
• Butyrate inhibits histone deacetylases (HDACs)9 — These enzymes modify histones, proteins around which DNA is wrapped, thereby influencing gene expression.
• HDAC inhibition manages brain inflammation — By inhibiting HDACs, butyrate induces epigenetic modifications that alter gene expression in brain cells,10 thereby decreasing the production of proinflammatory substances while simultaneously increasing the production of anti-inflammatory molecules, effectively dampening the inflammatory response in the brain.
Going deeper, a study published in Frontiers in Neuroscience provides a more nuanced look at butyrate's HDAC-limiting capabilities to help fight neuroinflammation associated with ischaemic stroke:11
"In addition to its role as an antitumor agent, butyrate partially achieves its anti- inflammatory effects by inhibiting HDAC.
For example, butyrate reduced neuroinflammation caused by microglia in IS [ischaemic stroke] mice by inhibiting HDAC, thereby altering the gene initiation of histone-3-lysine 9-acetylation (H3K9ac) in microglia. In conclusion, butyrate modulates microglia in the brain to attenuate neuroinflammation in IS through multiple mechanisms."
• Butyrate lowers the risk of Alzheimer's disease — Another study, which used animal test models of Alzheimer's disease, demonstrated that butyrate reduces the accumulation of amyloid-beta plaques, a pathological hallmark of the disease, and concurrently improves cognitive function. In fact, it was able to reduce amyloid-beta plaques by as much as 40%.12
• GLP-1 stimulation by butyrate helps fight against Parkinson's disease — Animal models have shown butyrate to have protective effects by stimulating glucagon-like peptide-1 (GLP-1).13 GLP-1 and GLP-1 receptor agonists (medications that mimic GLP-1) are being actively studied as potential treatments for Parkinson's disease because they appear to have neuroprotective effects.
In addition to reducing brain inflammation, research has shown that GLP-1 protects dopamine-producing neurons, which are damaged in Parkinson's disease, by reducing oxidative stress and improving mitochondrial function. GLP-1 also:
• Enhances autophagy — The cell's natural cleaning process that removes damaged proteins and cellular components. This is particularly important because Parkinson's disease involves the accumulation of misfolded proteins (especially alpha-synuclein).14,15
• Boosts metabolic function — Improves insulin sensitivity and cellular energy metabolism in the brain,16 which is often impaired in Parkinson's disease. Better energy metabolism helps neurons function more effectively and resist damage.
The Role of Butyrate in Neurotransmitter Function and Mood
Neurotransmitters are chemical messengers that transmit signals between nerve cells (neurons) in the brain, orchestrating a vast array of brain functions, including mood, behavior, cognition, sleep and appetite. And based on published evidence, butyrate (as well as other SCFAs) influences the production, release and signaling of several key neurotransmitters, including GABA (gamma-aminobutyric acid) and dopamine.17
• GABA is the primary inhibitory neurotransmitter in your brain — It acts as a natural calming agent by reducing neuronal excitability, promoting relaxation, and alleviating anxiety.18
Butyrate and other SCFAs have been shown to enhance GABA production in the gut, and remarkably, research has shown that GABA helps modulate abdominal pain and bowel disorders, showcasing the symbiotic relationship of the gut-brain axis.19
• Dopamine controls your reward responses — A neurotransmitter associated with motivation, movement and pleasure, dopamine is also modulated by butyrate. Butyrate crosses the blood-brain barrier to enhance its production, as well as microglial function and development.20
By modulating these vital neurotransmitter systems, butyrate exerts a significant influence on mood disorders such as anxiety and depression. Research has shown a link between altered gut microbiota composition, reduced butyrate production and the development of these conditions.21