By Ross Pelton

Scientific Director, Essential Formulas

Ross Pelton is a pharmacist, nutritionist, author and a health educator who is widely recognized as the world’s leading authority on drug-induced nutrient depletions. He was named one of the top 50 most influential pharmacists in the United States by American Druggist magazine for his work in Natural Medicine.

The Wide-Ranging Benefits of Butyrate

By Ross Pelton, RPh, PhD, CCN
Scientific Director, Essential Formulas

Butyrate is a postbiotic metabolite produced by some strains of probiotic bacteria when they ferment non-digestible dietary fibers in the colon. Studies have documented that Butyrate, a short-chain fatty acid (SCFA), plays an essential role in regulating many health aspects. Butyrate is so critical that the authors of one study called it The Butyrate Revolution.i In this article, I will summarize and explain the many benefits of Butyrate and provide tips on how you can increase Butyrate’s production in your microbiome.

Butyrate Provides 10% of Your Daily Energy Needs.

The cells that line your gastrointestinal tract are a layer of 1-cell thick epithelial cells. In the colon, epithelial cells are also known as colonocytes. These cells have the highest turnover rate in the body; humans make an entirely new lining of the intestinal tract every 4 to 6 days. It takes an enormous amount of energy to renew all of these cells continually. Studies have revealed that about 10% of a human’s daily energy needs are required for the constant creation of new epithelial cells. The energy for this cellular renewal process does not come from the food you eat. It comes to the postbiotic metabolite butyrate, which is the primary source of energy for the renewal of the cells that line your intestinal tract.ii Butyrate’s benefits include the following:

Anti-Inflammatory Activity

The cells in the lining of the GI tract of people with dysbiosis are frequently inflamed. Butyrate has been shown to provide significant anti-inflammatory activity.iii

Accelerating Colonocyte Renewal

Butyrate’s anti-inflammatory activity, coupled with the fact that it is the primary source of energy for colonocytes, enables it to accelerate protein synthesis, which results in the growth of healthy new colonocytes.iv Accelerating healthy new colonocytes’ growth to replace old inflamed cells is a critical part of the healing process for individuals with dysbiosis.

Butyrate Regulates Immune Function

In animal and human studies, Butyrate has been shown to enhance macrophages’ activity, which in turn, regulates immune function. Butyrate-activated macrophages are more effective at lowering inflammation and directly killing pathogens. The authors of one study stated that Butyrate makes macrophages “Go Nuclear” against bacterial pathogens.v

Healing Leaky Gut

By increasing the production of epithelial cell tight junction proteins, Butyrate has been shown to protect and aid in the repair of cellular tight junctions. Thus, Butyrate plays a role in healing the condition known as leaky

Butyrate and Skin Health

Studies have shown that Butyrate also influences the gut-skin axis and functions as a regulator of the skin immune system.vii In addition to providing energy for the renewal of healthy colonocytes and reducing oxidative stress, Butyrate also communicates with regulatory T-cells (T-Regs), which offers an anti-inflammatory activity that extends beyond the GI tract. Butyrate also stimulates the synthesis of collagen, which is an important structural component of skin.viii

Butyrate and the Brain

Butyrate-brain research conducted in animals suggests that Butyrate may have broad and significant effects on brain health. For example, when mice administered Butyrate, there is evidence of increased generation of new neuronsix, reduced oxidative stress and accelerated recovery following brain injuries.x

The Butyrate Paradox: Can Butyrate be Toxic?

Due to increased awareness of the importance of Butyrate, several companies are now selling oral butyrate supplements. But, increasing butyrate levels may not always be a good thing. Several studies have been published referring to the “Butyrate Paradox.”

In a healthy colon, Butyrate stimulates healthy new cells, which supports the renewal of the intestinal lining every 4 to 6 days. However, in an animal study, increasing butyrate levels in mice with colitis resulted in increased disease activity and a greater death rate than healthy controls.xi Therefore, it may not be appropriate to boost butyrate levels in people with dysbiosis or other gut inflammatory conditions such as ulcerative colitis.

The Fiber Gap

A lack of dietary fiber, referred to as The Fiber Gap, is increasingly being linked to depletion of the human gut microbiome and the astronomical rise in the incidence of chronic diseases.xii Studies have reported that approximately 90% of American children and adults DO NOT consume the recommended daily amount of dietary fiber.xiii

Because the diet of most Americans is severely deficient in the quantity and diversity of fiber, we can assume that most Americans’ microbiome is not producing adequate amounts of postbiotic metabolites, especially Butyrate.

How to Increase Butyrate

Only a few human-butyrate supplementation clinical trials have been conducted, and the outcomes have been inconsistent. Hence, at this time, I do not feel comfortable making butyrate supplementation recommendations.

The safest, the most effective way to increase the production butyrate is for people to let their microbiome do it naturally. To be effective, this involves the following two steps:

  1. Take Dr. Ohhira’s Probiotics daily, which delivers probiotics, prebiotics, and over 500 postbiotic metabolites is a very effective way to improve the composition of your microbiome.
  2. Increase the consumption of a diverse range of different types of fiber-rich foods. This enables an individual’s innate probiotic bacteria to ferment the dietary fibers and increase Butyrate’s production naturally.xiv

i Brouns F, et al. Resistant starch and “the butyrate revolution.” Trends in Food Science & Technology. 2002 Aug;13(8):251-261.
ii Bergman EN. Energy contributions of volatile fatty acids from the gastrointestinal tract in various species. Physiol Rev. 1990 Apr;70(2):567-90.
iii Couto MR, et al. Microbiota-derived butyrate regulates intestinal inflammation: Focus on inflammatory bowel disease. Pharmacol Res. 2020 Sep;159:104947.
iv Frankel W, et al. Butyrate increases colonocyte protein synthesis in ulcerative colitis. J Surg Res. 1994 Jul;57(1):210-214.
v Lobel L and Garrett WS. Butyrate Makes Macrophages “Go Nuclear: against Bacterial Pathogens. Immunity. Feb 2019;50(2):275-278.
vi Knudsen KEB et al. Impact of Diet-Modulated Butyrate Production on Intestinal Barrier Function and Inflammation. Nutrients. 20189 Oct 13;10(10):1499.
vii Schwarz A, et al. The Short-Chain Fatty Acid Sodium Butyrate Functions as a Regulator of the Skin Immune System. J Invest Dermatol. 2017 Apr;137(4):855-864.
viii Karna, E., et al. The mechanism of butyrate-induced collagen biosynthesis in cultured fibroblasts. Acta Pol. Pharm. 2009;66: 129–134.
ix Kim HJ, et al. The HDAC inhibitor, sodium butyrate, stimulates neurogenesis in the ischemic brain. J Neurochem. 2009 Aug;110(4):1226-40.
x Li H, et al. Sodium butyrate exerts neuroprotective effects by restoring the blood-brain barrier in traumatic brain injury mice. Brain Res. 2016 Jul;1642:70-78.
xi Zhang, Q. et al. Accelerated gut microbiota dysbiosis during aggravation of DSS-induced colitis by a butyrate-producing bacterium. Sci. Rep. 6, (2016).
xii Deehan EC and Walter J. The Fiber Gap and the Disappearing Gut Microbiome: Implications for Human Nutrition. Trends in Endocrinology & Metabolism. 2016 May;27(5):239-242.
xiii Clemens R. et al. Filling America’s Fiber Intake Gap: Summary of a Roundtable to Probe Realistic Solutions with a Focus on Grain-Based Foods. Journal of Nutrition. 2012 July; 142(7): 1390S-1401S.
xiv Zhao L, et al. Gut bacteria selectively promoted by dietary fibers, alleviate type 2 diabetes. Science. 9 Mar 2018;359(6380): 1151-1156.


By Ross Pelton, RPh, PhD, CCN
Scientific Director, Essential Formulas

Ross Pelton is a pharmacist, nutritionist, author and a health educator who is widely recognized as the world’s leading authority on drug-induced nutrient depletions. He was named one of the top 50 most influential pharmacists in the United States by American Druggist magazine for his work in Natural Medicine.

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