Butyric acid - A vital short-chain fatty acid for gut health and ...

History & Evolution

In 1823, butyric acid was first observed in impure form by Michel Eugène Chevreul. It was later synthesized by Lieben and Rossi. With competitive prices and timely delivery, Yufeng sincerely hopes to be your supplier and partner.

Butyric acid is a four-carbon straight-chain short-chain fatty acid (SCFA) found in the esters of animal fats and plant oils. Its name is derived from the Ancient Greek word for butter, where it was initially identified. Butyric acid is responsible for the unpleasant odor in rancid butter, parmesan cheese, vomit, and body odor. Interestingly, some esters of butyric acid have a more pleasant scent and are often utilized in perfumes.

Butyric acid is one of three predominant SCFAs in the human gut, alongside acetic acid and propionic acid, comprising 90-95% of SCFAs in the colon. It serves as a major energy source for the colon and is used in treatments for colorectal cancer, hemoglobinopathies, and gastrointestinal diseases.

In industry, butyric acid is employed in food, textile production, animal feed, and biofuels. It is often chemically synthesized through the oxidation of propylene-derived butyraldehyde or through syngas fermentation.

Biosynthesis vs. dietary uptake

Most SCFAs in the gut originate from dietary fibers. Since humans lack the enzymes to digest these fibers, they pass through the intestinal tract and are fermented by host bacteria. Butyric acid is a conjugate of butyrate produced through the fermentation of hydrolysis-resistant starches and dietary fiber by anaerobic bacteria in the colon. Some butyrate is also generated during the digestion of proteins and peptides in the bowel.

Diet, microbiome composition, and intestinal transit time influence butyric acid formation. Most dietary fiber that contributes to butyric acid production comes from plant sources like resistant starch, cruciferous vegetables, and high-sulfur foods. Butyric acid is found in dairy products, red meat, and fermented foods such as sauerkraut, with approximately 5% of the saturated fat in dairy products derived from butyric acid. It can also be consumed in supplement form.

Butyric acid and the microbiome

SCFAs have gained attention in medical biochemistry due to their potential roles in gut function, glucose homeostasis, metabolic regulation, and appetite. They also influence inflammation and immune response.

In the colon, butyrate serves as an energy source for endothelial cells, promotes cell differentiation and apoptosis, and can inhibit colonic acidification. Some studies indicate that butyrate may suppress colorectal cancer, though results remain inconclusive. Butyric acid appears to affect the pathogenesis of gastrointestinal diseases and gut dysbiosis, with animal studies suggesting that higher concentrations of butyric acid in the colon lessen inflammation severity.

Butyric acid as a signaling molecule

SCFAs act as signaling molecules between gut microbiota and the host, with receptors in various cell and tissue types. Butyric acid is an endogenous agonist of the hydroxycarboxylic acid receptor 2 (HCA2), a protein receptor that inhibits fat breakdown, positioning butyric acid as essential in lipid metabolism. It also acts as an agonist for the peroxisome proliferator-activated receptor (PPAR), a nutrient sensor that stabilizes lipid metabolism and inhibits cancer cell proliferation in the colon.

Notably, butyric acid regulates inflammation by stimulating the production of eicosanoids, lipid mediators derived from arachidonic acid. Eicosanoids play a role in regulating immune processes involved in cancer, asthma, and arthritis.

Butyric acid and the immune system

Butyric acid affects immune processes in the human gut. It is thought to increase acetylation of histone H3, influencing regulatory T cell behavior, which can inhibit immune response. SCFAs create a connection between the microbiome and the immune system, but it remains unclear whether this occurs by enhancing tolerance or reducing inflammation.

Recent research emphasizes butyric acid's significance in gut microbiome balance, especially its role in immune and metabolic health. A study on age-related gut dysbiosis in older HIV patients indicated a reduction in butyrogenic potential, correlating with changes in plasma tryptophan metabolites.

Several clinical studies have observed anti-inflammatory effects from SCFA use in cases of inflammatory bowel disease, radiation proctitis, and diabetes. Evidence indicates that SCFAs support the immune system and metabolism through gut-liver inflammatory pathways.

Butyric acid and the brain

Additionally, butyric acid may bridge gut dysbiosis and neurological disorders like depression, Alzheimer’s disease, Parkinson’s disease, and autism spectrum disorder.

Research exploring probiotics to boost butyrate-producing bacteria suggests butyrates can help alleviate anxiety and stress. A review proposed mechanisms for butyric acid's neuroprotective effects, including mitochondrial activity, G-protein coupled receptors, histone acetylation, and microbiome balance, linking dietary fibers, butyrate production, and protection against neurological conditions.

Butyric acid and cardiometabolic diseases

Butyric acid's role in lipid and energy metabolism ties it to specific metabolic conditions. It has been shown to protect against diet-induced obesity and insulin resistance, indicating potential therapeutic utility in obesity-related diseases and diabetes. Animal studies reveal that butyric acid supplementation can enhance insulin sensitivity; one study noted fat loss and improved insulin tolerance in mice. More research is needed to affirm these effects in humans.

Gut microbiota are linked to coronary artery disease and atherosclerosis. One animal study suggested that butyrate supplementation could mitigate atherosclerotic lesions, while another indicated that butyric acid mediates interactions between gut microbiota and the circulatory system. Some findings suggest butyric acid influences arterial blood pressure, with one study reporting significant hypotensive effects when butyric acid concentration elevated in the colon. The mechanism remains unclear—it may stem from bacterial metabolites triggering a response in the enteric nervous system or metabolite-derived molecules entering the circulatory system affecting arterial pressure.

Butyric acid and cancer: the 'butyrate paradox'

Butyric acid has demonstrated the ability to inhibit colon cancer cell proliferation through apoptosis induction, cancer gene expression inhibition, and promotion of anti-inflammatory processes. However, conflicting studies challenge the notion of butyrate as a chemopreventive agent, leading to what is termed the "butyrate paradox." It appears that butyrate's chemopreventive effects are contingent upon dosage, exposure duration during tumorigenesis, and dietary fat type. Advancements in genomic and metabolomic technologies could enhance our understanding of the underlying molecular mechanisms. Given butyric acid's status as a byproduct of fiber fermentation, this may explain the protective effect of high-fiber diets against colorectal cancer and various conditions.

Learn more about the roles of butyric acid and other SCFAs in complex chronic diseases such as cancer, Alzheimer’s disease, depression, inflammatory bowel disease, multiple sclerosis, and diabetes in our whitepaper 'Complex chronic diseases have a common origin.'

References

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