Butyrate (from the Ancient Greek word for "butter") is a short-chain fatty acid (SCFA) that occurs naturally in butter and other foods and is also produced by microbes in the gut. Microbial production of short-chain fatty acids, which also include acetate and propionate, occurs in the colon during the fermentation of indigestible fibers found in plant foods such as legumes, fruits, nuts, cereals, and whole grains. In the gut, butyrate is the preferred fuel source for colonocytes, the skin-like cells that line the colon.[1]

Butyrate participates in a wide array of metabolic pathways in the body. Accordingly, low concentrations of butyrate in the blood, colon, liver, and brain have been identified in a diverse collection of diseases. Generally, increasing butyrate levels has been shown to have beneficial effects on health. More specifically, research supports the role of butyrate in the following:

  • Reduced intestinal permeability (i.e., leaky gut) – Greater levels of butyrate oxidation in the gut were associated with lower colonic permeability in ulcerative colitis.[2]
  • Increased neurogenesis – Butyrate enhances neurogenesis directly.[3]
  • Improved glucose tolerance – The microbiota of people with type two diabetes shifts away from butyrate-producing species.[4]
  • Reduced inflammation – Butyrate promotes regulatory T cell maturation.[5]

Beta-hydroxybutyrate (BHB) is a ketone body that can be synthesized from butyrate, dietary fats, body fat, or ketogenic amino acids. Endogenous (i.e., produced by the body) ketones, which include acetone and acetoacetate in addition to beta-hydroxybutyrate are a main source of cellular energy when glucose availability is low. Ketones increase in concentration in the brain, liver, heart, muscle, and other tissues during exercise, fasting, and carbohydrate restriction on a ketogenic diet.[6]

Research demonstrating strategies to increase butyrate and BHB includes:

  • Omega-3 fatty acid consumption increased the concentration of butyrate-producing bacteria in the gut.[7]
  • Aerobic exercise training increased butyrate-producing bacteria in the gut independent of diet.[8]
  • Time-restricted eating remodeled the gut microbiota, increasing the rate of butyrate production from bacteria such as Lachnospiraceae family.[9]
  • A fasting-mimicking meal replacement bar that was high in fat and low in carbs extended the ketogenic benefits of a 15-hour overnight fast and increased serum concentrations of BHB.[10]
  • Endurance exercise, but not strength training, increased the concentration of BHB in the muscles of aged mice. BHB levels improved skeletal muscle growth and cognitive function.[10]

Summaries

Below is a selection of summaries from current research investigating the role of butyrate in health and disease.

Exercise training changes the gut microbiome, enhancing butyrate metabolism.

A healthy gut microbiota contains a diverse population of bacterial species, each with its own metabolic requirements. Butyrate is an important fuel source for human cells and microbes in the gut; however, not all bacteria can produce butyrate. Bacterial genera that possess butyrate-producing genes such as Faecalibacterium and Lachnospira are vital to supporting a healthy gut ecosystem. Findings of one report demonstrate the ability of exercise training to increase butyrate-producing microbes in the gut.

The researchers recruited 18 adults with a overweight BMI and 14 adults with a lean BMI. Participants completed six weeks of supervised endurance exercise training (30-60 minutes, three times per week) and then six weeks of sedentary activity. The researchers collected a stool sample before the exercise training period, after the exercise training period, and ater the sedentary activity period.

Overall, exercise increased the concentration of butyrate-producing microbes in the gut microbiota and the expression of butyrate-producing genes by those microbes. Exercise increased the concentration of SCFAs in stool from participants with a lean BMI, but not participants with obesity. Exercise-induced changes to the gut microbiota mostly reversed over the six-week sedentary period.

These results demonstrate the responsiveness of the gut microbiota to beneficial changes in behavior. Specifically, exercise increases butyrate production in the gut, which may reduce chronic disease risk.

Gut bacteria may alter the brain aging through the production of butyrate.

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 change the trajectory of brain aging.

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 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.

Frequently asked questions

What dietary and lifestyle factors can improve symptoms of leaky gut (i.e., increased intestinal permeability)?

Early evidence supports the consumption of dietary fiber and some probiotic-containing foods and supplements for improving symptoms of leaky gut.[11] Some of the mechanisms involved in this improvement may involve increased butyrate production in the gut. Specific information regarding nutrients and dose can be found in this review.

How can I increase butyrate/BHB while fasting or eating a ketogenic diet?

Consuming an exogenous ketone supplement increases serum concentrations of BHB; however, these supplements can have a very unpleasant smell/taste. Some evidence suggests that medium chain triglycerides (MCTs) may increase serum BHB levels in a dose-dependent manner, meaning the more MCTs consumed, the greater the rise in BHB levels. However, these is a lot of variation from person to person.[12]

Topics pages

  • Beta-hydroxybutyrate is an endogenous ketone compound derived from butyrate and lipids. Beta-hydroxbyutyrate is a source of cellular energy and can be converted to other cellular energy carriers such as nicotinamide adenine dinucleotide (NAD+).

  • Intestinal permeability is directly modulated by butyrate produced via fermentation of dietary fiber by gut microbes, strengthening barrier integrity and reduces the risk of disease.

Episodes

  1. ^ Intestinal development and differentiation Exp Cell Res 317, no. 19 (November 2011): 2702–10.
  2. ^ In vivo colonic butyrate metabolism and colonic permeability in extensive ulcerative colitis Gastroenterology 117, no. 3 (September 1999): 745–46.
  3. ^ Neurogenesis and prolongevity signaling in young germ-free mice transplanted with the gut microbiota of old mice Science Translational Medicine 11, no. 518 (November 2019). https://doi.org/10.1126/scitranslmed.aau4760.
  4. ^ Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases Nature Genetics 51, no. 4 (February 2019): 600–605. https://doi.org/10.1038/s41588-019-0350-x.
  5. ^ Malformed reference
  6. ^ Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body -hydroxybutyrate eLife 5 (June 2016). https://doi.org/10.7554/elife.15092.
  7. ^ Long-term monitoring of the human intestinal microbiota composition Environmental Microbiology 15, no. 4 (April 2013): 1146–59. https://doi.org/10.1111/1462-2920.12023.
  8. ^ Exercise Alters Gut Microbiota Composition and Function in Lean and Obese Humans Medicine & Science in Sports & Exercise 50, no. 4 (April 2018): 747–57. https://doi.org/10.1249/mss.0000000000001495.
  9. ^ Beneficial gut microbiome remodeled during intermittent fasting in humans Rejuvenation Research , May 2021. https://doi.org/10.1089/rej.2021.0025.
  10. ^ a   b An Intermittent Fasting Mimicking Nutrition Bar Extends Physiologic Ketosis in Time Restricted Eating: A Randomized, Controlled, Parallel-Arm Study Nutrients 13, no. 5 (April 2021): 1523. https://doi.org/10.3390/nu13051523.
  11. ^ What to do about the leaky gut Gut 71, no. 2 (September 2021): 424–35. https://doi.org/10.1136/gutjnl-2021-325428.
  12. ^ Assessing the Impact of Factors that Influence the Ketogenic Response to Varying Doses of Medium Chain Triglyceride (MCT) Oil The Journal of Prevention of Alzheimer s Disease , 2020, 1–10. https://doi.org/10.14283/jpad.2020.53.

Topics related to Butyrate

view all
  • Time-restricted eating
    Time-restricted eating is a form of daily fasting wherein a person eats only during a limited time window, typically 8- to 12-hours.
  • Intestinal permeability
    Intestinal permeability determines how well the GI tract absorbs nutrients and excludes dangerous particles from the environment such as pathogens and toxins.
  • Aerobic exercise
    Aerobic exercise, physical activity that increases breathing and heart rate, promotes cardiovascular, brain, and whole-body health.
  • Beta-hydroxybutyrate
    Beta-hydroxybutyrate (BHB) is a ketone body and source of cellular energy produced via the breakdown of fats during times of carbohydrate scarcity and fasting.
  • Fasting
    Fasting – the voluntary abstinence from food and drink – is an ancient practice now widely appreciated for its beneficial effects on healthspan.