Short-Chain Fatty Acids: Strengthen the Gut-Brain Health Connection with Butyrate

Kara Fitzgerald, ND

3 years ago

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Key Points:

All SCFAs have wide-ranging therapeutic benefits, but in this article we’ll focus on butyrate as a therapeutic agent for gut and brain health.
Butyrate is the food for the colonocytes, the thin layer of cells that comprises the lining of the large intestine. Within the intestinal environment, it protects and supports the mucosa, gut motility, and the commensal bacteria of the colon.
Although butyrate is largely present in the gut, it can also have effects on the brain via the gut-brain axis, as well as by lowering inflammation, stabilizing DNA structure, and sequestering harmful metabolic by-products like ammonia.
When supplementing butyrate, it’s important to choose a product tested for purity and quality, and one that provides the best value at a reasonable cost for consumers.

The Many Roles of Short-Chain Fatty Acids

Several lines of evidence suggest that brain function, behavior and immune functioning are influenced greatly by microbial metabolites [1, 2, 3]. One of the key metabolites of the microbiota is the short-chain fatty acid (SCFA), butyrate.

Butyrate is a four-carbon fatty acid produced in the gut via the bacterial fermentation of dietary fiber, primarily resistant starch. Butyrate, along with other fermentation-derived short-chain fatty acids like acetate and propionate, and the structurally related ketone bodies acetoacetate and β-hydroxybutyrate, show promising effects in a myriad of diseases like obesity, colorectal cancer, diabetes, inflammatory bowel disease, and mental health disorders.

These SCFA molecules are multifaceted. Some of them stay local, exerting their beneficial effects in the gut, while others act as long-distance signaling molecules, taking part in complex interactions that affect our physiology elsewhere in the body. Acetate, propionate, and butyrate account for approximately 90 to 95% of the SCFAs in the gut, mostly present in the colon but also in the small intestine.

Growing interest in gut health and its connection to the brain via the bi-directional vagus nerve pathway has spawned curiosity in the butyrate molecule as well. At BodyBio we have learned from both emerging research and the firsthand experience of many practitioners using our butyrate with their patients that it can have a significant beneficial impact on both gut and brain health.

Butyrate Basics and Benefits

Of the short-chain fatty acids we mentioned above, butyrate specifically is the major energy source for the colonocytes, the cells that line our colon. Normally our microbiome produces butyrate endogenously through the fermentation of resistant starches such as cooled rice, potatoes, beans, and whole grains. We can also get smaller amounts from dairy, if it is tolerated, and some dietary fibers.

However, many people are not able to digest dairy or the substantial amounts of resistant starch needed to produce enough butyrate in the colon. In these cases, supplemental butyrate is a sensible companion.

Within the gut, butyrate is able to influence the microbiome environment as well as the physical structure and motility of the gut. Healthy butyrate levels encourage good gut function, nutrient absorption, a balanced microbiome, and various host-signaling mechanisms.

Butyrate is also key in modulating mucosal inflammation and reducing oxidative stress, regulating transepithelial fluid transport, and reinforcing the epithelial defense barrier. It has been implicated in a number of studies to prevent and inhibit colorectal cancer [15, 16, 17]. Beyond the gut environment, butyrate may be useful for many other conditions such as metabolic dysfunction, diabetes, autoimmune disorders, neurological conditions, and insulin resistance.

A Closer Look at Butyrate and Intestinal Health

In functional medicine, we know that one of the first places practitioners look to identify root cause issues is the gut, specifically whether the patient has a leaky gut. To seal and heal a leaky gut, there is no better therapeutic molecule than butyrate, the natural fuel source for the colonic epithelial layer.

Intestinal Barrier Integrity

Butyrate is quite literally the food for the gut lining. The enterocytes that line the gut wall are endothelial cells and constitute a layer that is only a single cell thick, forming the semi-permeable gut lining. Butyrate keeps this lining functioning optimally, allowing nutrients through to the bloodstream and keeping waste and pathogens out.

By design, colonocytes live less than a week and then are replaced by new ones. Because of this high turnover rate, harsh cleanses are not necessary. But proper levels of butyrate are vital to maintaining a healthy microbiome and supporting your gut health, reducing inflammation, modulating oxidative stress, and inhibiting colon cancer cell growth.

Additional Butyrate Gut Benefits

Butyrate supports the gut lining. Having a healthy gut lining supports a healthy microbiome because the immune system in the gut lining has a large role to play in pruning and shaping the microbes that reside there. This in turn, helps to lower inflammation and nourish a healthy microbiome. While improving this physical structure, butyrate can also complement probiotic therapy as patients work to restore balance to the commensal bacteria in the colon. Research shows that the absence of the bacteria efficient at fiber digestion and SCFA production, leading to decreased SCFA levels, is associated with colonic diseases, including irritable bowel disease such as Ulcerative Colitis and Crohn’s.

SCFAs also have nutritive effects on the colonic mucosa. Butyrate’s other actions in the colon include increasing protective mucin production (which lubricates and protects the linings of the body cavities), blood flow, muscle activity and absorption of water and salt.* Furthermore, SCFAs reduce luminal pH in the colon, which inhibits pathogenic microorganisms and may stimulate mineral absorption through increased solubility.

Appropriate levels of butyrate are key, not only to digestion, but to cellular health, DNA health, and as we’ll look at next, brain health.

Butyrate and the Gut-Brain Connection

There are several ways that butyrate supports the brain via the gut, including histone deacetylase inhibition, increasing brain-derived neurotrophic factor, calming inflammation and more.

HDAC inhibitor: Butyrate can play a regulatory role which can influence gene expression as it inhibits enzymes like histone deacetylase that deleteriously unwind DNA. In some cases, when left unchecked, this may cause critical illness.

Effects on Ammonia Levels: Butyrate also sequesters harmful ammonia that forms from faulty protein metabolism and/or from inborn metabolic errors. Ammonia can be a byproduct of bacterial overgrowth in the gut, making butyrate a potentially-helpful palliative intervention even as you work on the underlying conditions. It’s role in this and as an HDAC inhibitor have benefits for mental clarity and brain health.

Brain-derived neurotrophic factor (BDNF): Based on pre-clinical data, Butyrate may increase brain-derived neurotrophic factor, helping to clear mental fog and promote neurotransmitter regulation and brain plasticity.

Anti-inflammatory: The fiery process of inflammation is linked to most chronic disorders, from heart disease to arthritis to type 2 diabetes. Certainly the same is true for neurological disease and psychological conditions like depression and anxiety. Inflammation fuels a cytokine known as interleukin-6 (IL-6), which remains elevated in chronic sickness.

Butyrate is a rescue molecule in inflammatory diseases, impairing the oxidative processes that stir up inflammation. When inflammation is cooled at the source of chronic disease, the gut, the whole-body inflammatory response improves, including in the brain.

Sleep: Research also suggests that butyrate enhances sleep, serving as a sleep-promoting signal from the gut to the brain. Oral administration resulted in a 50% increase in non-rapid eye movement (NREM) sleep in mice within four hours of treatment.

Myelination: One preclinical animal study investigated butyrate’s effects on myelination; researchers found that butyrate both suppressed demyelination and enhanced remyelination in oligodendrocyte cells. Myelin is an electrical insulator that speeds the conduction of nerve impulses. This shows that butyrate not only affects the processes of the brain, but the physical cells themselves.

How to Source a Quality Butyrate Supplement

There are a few different types of butyrate supplements available on the market. You’ll find:

IV sodium phenylbutyrate
Oral sodium phenylbutyrate (typically only available through a specialty pharmacy)
Butyric acid + mineral salt
Butyric acid + triglyceride (tributyrin)
Butyric acid + lipid.

The first option, IV sodium phenylbutyrate, is not easily accessible for most people, not to mention costly and more challenging to administer. The second can be very difficult to find.

At BodyBio we start with butyric acid which, as an acid, has a low pH so we compound it with an alkali, a combination that forms a salt + water. At this stage, we no longer have butyric acid, but butyrate, a buffered form of butyric acid. Our ingredients are simple and effective and have been trusted for over 25 years by physicians.

From there, BodyBio provides three options for butyrate supplements: calcium magnesium butyrate, which we recommend for most people due to common deficiency in these minerals; sodium potassium butyrate; and sodium butyrate, for those who may need more support with these minerals, such as athletes. All three options are pure, quality-tested, and backed by thousands of customer reviews stating their powerful therapeutic effects.

Butyrate for Gut and Brain Health

When we look at the numerous effects of butyrate, a microbiome-derived metabolite, on the body and mind, it becomes evident just how interconnected gut health and brain health are. But for those who need extra support to repair their gut, butyrate can be a key player in ameliorating gastrointestinal conditions, calming inflammation, restoring gut function and integrity, and improving brain health. Supplemental butyrate can provide the extra boost to restore a healthy gut and create a resilient microbiome.

Learn more about BodyBio Butyrate here.

Additional Research

References

Dr. Thomas Wnorowski, PhD

Dr. Wnorowski is a widely published biomedical nutritionist, Board Certified in Integrative Medicine, with post-doctoral study from Purdue, Tufts and Johns Hopkins Universities, focusing on the clinical management of obesity, diabetes education, men’s and women’s health and cardiac rehabilitation. He has a PhD and certifications in clinical/biomedical nutrition and master’s degrees in human nutrition and educational psychology. A member of the Academy of Nutrition and Dietetics and the American Association of Integrative Medicine, he sits on the board of Mohr Results Sports Nutrition and the Integrative and Function Nutrition Academy. Dr. Wnorowski was the honored recipient of the 2006 Excellence in Practice Award from the American Dietetic Association.