Butyrate
Beta-hydroxybutyrate featured article
Background
Beta-hydroxybutyrate (BHB) is an endogenous (i.e., produced by the body) ketone produced via the breakdown of fats during times of carbohydrate scarcity (e.g., during fasting, exercise, or carbohydrate-restricted/ketogenic diets). BHB is produced from butyrate, a short-chain fatty acid produced by the gut microbiota via the fermentation of dietary fiber. Along with the ketones acetone and acetoacetate, BHB serves as a source of cellular energy.
BHB is a small energy-carrying molecule that can convert to other energy carriers such as acetyl-CoA, succinyl-CoA, and nicotinamide adenine dinucleotide (NAD+). BHB is also a signaling molecule involved in basic metabolic processes in various cell types.
**Evidence suggests BHB...
Episodes
Topic Pages
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Beta-hydroxybutyrate
Both four-carbon metabolites inhibit class I HDACs and activate FFAR3/HCAR2, but β-hydroxybutyrate arises from hepatic ketogenesis.
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Butyrate
Butyrate is a four-carbon short-chain fatty acid produced by gut microbiota, serving as colonocyte energy and histone deacetylase inhibitor.
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Intestinal permeability
Butyrate enhances epithelial barrier integrity by upregulating tight-junction proteins and promoting mucosal repair, thereby reducing intestinal permeability.
News & Publications
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Gut barrier dysfunction impairs butyric acid uptake into the blood – potentially increasing the risk of carotid atherosclerosis. www.nature.com
Poor gut barrier function may contribute to carotid atherosclerosis – a narrowing of the blood vessels that supply the brain – according to a new study. People with carotid atherosclerosis demonstrated increased markers of gut barrier damage and inflammation, both of which impair butyric acid uptake into the blood.
Researchers conducted a study involving 43 people with carotid atherosclerosis and 44 healthy people. They measured butyric acid levels in the participants' blood and feces and assessed their gut health and inflammation.
The people who had carotid atherosclerosis had higher levels of butyric acid in their feces but not in their blood, despite robust gut microbial production of butyric acid. They also had higher levels of markers that indicate gut barrier damage and inflammation and tended to be heavier, carry more weight around their waist, have poor blood glucose control, and have higher markers of inflammation.
The researchers hypothesized that the participants' higher fecal (but not blood) levels of butyric acid were due to poor gut barrier function, which could impair butyric acid absorption and in turn reduce its uptake into the blood. Other research has found that high fecal levels of butyric acid are associated with intestinal permeability, obesity, metabolic dysfunction, and high blood pressure.
Butyric acid, a short-chain fatty acid, is best known for its roles in maintaining gut barrier function and preventing intestinal permeability. However, butyric acid also protects the vascular endothelium – the lining of the blood vessels. Having low butyric acid levels in the blood could contribute to the risk of developing carotid atherosclerosis.
[Learn about butyrate, a compound related to butyric acid, in our overview article.] (https://www.foundmyfitness.com/topics/butyrate)
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Butyrate receptor in colon functions as tumor suppressor. aacrjournals.org
Butyrate, a short-chain fatty acid, may suppress colon cancer growth.
Colon cancer is one of the leading causes of death in developed nations. Health experts attribute much of the risks associated with colon cancer to dietary patterns, especially those that are high in red meat and low in fruits, vegetables, and fiber. Findings from a 2009 study suggest that butyrate, a short-chain fatty acid, activates a protein called GPR109A in the colon to suppress colon cancer.
Short-chain fatty acids are produced by the gut microbiota during the fermentation of dietary fiber. In turn, these fatty acids provide energy to cells in the colon and play key roles in maintaining gut health. Butyrate, in particular, functions as a tumor suppressor by inhibiting enzymes called histone deacetylases, which drive tumor growth.
The investigators assessed the production of GPR109A in the colon tissues of mice and humans (with and without colon cancer) using monoclonal antibodies that targeted the protein. Then they determined whether butyrate bound to GPR109A and how the fatty acid influenced tumor growth. Finally, they gauged the effects of butyrate on cancer cell growth and progression.
They found that GPR109A was present on the surface of cells in the colons of both mice and humans, where it recognized and bound with butyrate. In the setting of cancer, GPR109A activity was silenced, effectively shutting down its activity. Supplying butyrate switched on the activity of GPR109A, which in turn promoted the death of cancer cells and suppressed the activity of nuclear factor-κB, a transcription factor that drives inflammation and tumor growth.
These findings suggest that GPR109A mediates the tumor-suppressive effects of butyrate in the colon. Interestingly, evidence indicates that beta-hydroxybutyrate, a type of ketone, also binds with GPR109A, suggesting that the compound exerts anticancer properties in the colon. Learn more about the beneficial health effects of butyrate and beta-hydroxybutyrate in our overview articles.
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Butyrate may protect against graft-versus-host disease after bone marrow transplants, suggests animal research www.sciencedaily.com
From the article:
In a new study, published in Nature Immunology, researchers searched for alterations in the gut microbiome to see whether their metabolites could impact outcomes after BMT.
They found that a metabolite called butyrate was significantly reduced in the intestinal tract of experimental mice that received bone marrow transplant. When the researchers increased butyrate in these mouse models, they saw a decrease in the incidence and severity of graft vs. host disease.
“Our findings suggest we can prevent graft vs. host disease by bolstering the amount of the microbiome-derived metabolite butyrate,” says study lead author Pavan Reddy, M.D., the Moshe Talpaz Professor of Translational Pathology and interim division chief of hematology/oncology at the University of Michigan.
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β-Hydroxybutyrate may be a substitute for butyrate in protecting from colon cancer: BHB activates a natural receptor involved in killing cancer cells www.sciencedaily.com
Currently selected for this coming member’s digest by team member Melisa B.
From the article:
Researchers report in the April issue of Cancer Research that the GPR109A receptor is activated by butyrate, a metabolite produced by fiber-eating bacteria in the colon. The receptor puts a double-whammy on cancer by sending signals that trigger cell death, or apoptosis, and shutting down a protein that causes inflammation, a precursor to cancer.
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That got the German research team to search for alternative activators of the receptor, resulting in identification of beta-hydroxybutyrate as a natural receptor activator. The same study showed butyrate also could activate the receptor but with much less potency. That got Dr. Ganapathy thinking about a place where butyrate levels were already high – the colon – which led to his discovery that the receptor was also on colon cells.
Butyrate plays other protective roles in colon cancer. In 2004, MCG researchers identified a gene, SLC5A8, that transports butyrate inside cells where it inhibits the enzyme HDAC, which gets upregulated in cancer to produce the uncontrolled cell growth that is a disease hallmark.
“If you block HDAC, you can kill the cancer cell,” Dr. Ganapathy says.
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Rebalancing gut microbiome with butyrate lengthens survival in mouse model of ALS by repairing intestinal permeability www.sciencedaily.com
From the article:
In a mouse model of ALS, the compound butyrate helped correct a gut microbiome imbalance and reduced gut leakiness – both symptoms of ALS. The treated mice lived also longer compared to mice that weren’t given butyrate.
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When the researchers fed the ALS-prone mice butyrate in their water, starting when the mice were 35 to 42 days old, the mice showed a restored gut microbiome profile and improved gut integrity. Butyrate-treated mice also showed improved neuromuscular function and delayed onset of ALS symptoms. Treated mice showed symptoms at 150 days old compared to control mice at about 110 days. Treated mice also lived an average 38 days longer than mice not given butyrate.
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Gut bacteria may alter the aging process of the human brain through the production of butyrate www.sciencedaily.com
The gut microbiota is a complex and dynamic population of microorganisms that is subject to change throughout an individual’s lifespan in response to the aging process. Findings from a new study demonstrate that altering the gut microbial population may alter the aging process of the human brain.
The authors of the study transplanted gut microbiota samples from healthy young or old mice into young germ-free mice. Eight weeks after the transplant, the mice that received microbial samples from the old mice demonstrated increased neurogenesis – the process of forming new neurons – in the hippocampus region of their brains.
Further analysis revealed that these mice also had larger numbers of butyrate-producing microbes in their colons. Butyrate, a short-chain fatty acid, is produced during bacterial fermentation in the human colon and has wide-ranging effects on human physiology. In this study, butyrate was associated with an increase in growth factors and subsequent activation of key longevity signaling pathways in the livers of the recipient mice. When butyrate alone was given to the recipient mice it promoted neurogenesis, as well.
The findings from this study may have relevance for dietary interventions to maintain or improve brain health.