Tributyrin

What is Tributyrin?

Tributyrin is a highly bioavailable, stable form of the short-chain fatty acid (SCFA) Butyrate, It is an ester composed of butyric acid and glycerol.

What is Butyrate?

Butyrate is normally produced by bacterial fermentation of resistant starches/ prebiotic fiber (from good commensal bacteria), but it is also found in butter, ghee, cheese, and dairy.

Butyrate is the main source of energy for the enterocytes and colonocytes of the digestive tract, and as such is a super important compound for gut health.

Butyrate has an anti-inflammatory action, acts on intestinal motility (constipation and diarrhea), stimulates the absorption of water and sodium, helps to maintain the protective mucus layer of the intestine, helps combat leaky gut and has also been shown to have positive effects on colon cancer.

What are the Benefits of Butyrate?

For the Gut:

Tributyrin/Butyrate keeps your colon cells healthy, reduces inflammation, boosts your immune system, and improves gut health by stimulating mucosal repair and providing more energy to the cells of the GI tract. Clinically, tributyrate/butyrate has several beneficial effects: – Crohn’s disease and ulcerative colitis autoimmune bowel diseases. – Irritable bowel syndrome (IBS) Tributyrtin enhances the colonic defense barriers by: – Increasing mucus production – Decreasing epithelial hyper-permeability by promoting tight junctions and tight junction repair – Increasing villus height and villus height: crypt depth (Wang et al. 2019) – Decreasing pH. – Tributyrin and probiotic Lactobacillus GG (LGG) minimise broad-spectrum antibiotic-induced loss of anion exchangers, butyrate transporter and receptors, and tight junction proteins.” (Cresci, Nagy & Ganapathy. 2013) -Preventing toxins from crossing the gut barrier.

For Inflamation:

– Histone deacetylase (HDAC) inhibitor.
– Inhibits the NFkB inflammasome, thereby protecting the DNA from reactive oxygen species.
– Cyclooxygenase 2 (COX-2) inhibition; reduces pro-inflammatory series 2 and 4 eicosanoids.
– Activates glutathione s-transferases (GST), an enzyme that aids in detoxification. GST speeds up the linking of toxic compounds with glutathione (GSH), thus forming a less reactive substance.
– Activates p53 transcription factor and activates p21 (cell cycle arrest); via these mechanisms and HDAC inhibition, studies have shown butyrate to prevent the progression of colon cancer in animal studies.
– Improves mitochondrial function. – Modulates the AMPK-mTOR

Butyrate Mechanisms

Binds to G protein receptors: GPR109A,GPR41, GPR43 on the cell membrane and is also transported intracellularly by sodium monocarboxylate transporter 1 SMCT1 and monocarboxylate transporter MCT1: (Na+ or H+ with Butyrate)

Butyrate Studies:

Cresci, G. A., Glueck, B., McMullen, M. R., Xin, W., Allende, D., & Nagy, L. E. (2017). Prophylactic tributyrin treatment mitigates chronic-binge ethanol-induced intestinal barrier and liver injury. Journal of gastroenterology and hepatology, 32(9), 1587–1597. https://doi.org/10.1111/jgh.13731

HM Hamer, D Jonkers, K Venema, S Vanhoutvin, FJ Troost, RJ Brummer. Review article: the role of butyrate on colonic function. Alimentary Pharmacology and Therapeutics. 2008, 27(104-119).

Miyoshi, M., Iizuka, N., Sakai, S., Fujiwara, M., Aoyama-Ishikawa, M., Maeshige, N., Hamada, Y., Takahashi, M., & Usami, M. (2015). Oral tributyrin prevents endotoxin-induced lipid metabolism disorder. Clinical nutrition ESPEN, 10(2), e83–e88. https://doi.org/10.1016/j.clnesp.2015.02.001

Mortensen, P. B., & Clausen, M. R. (1996). Short-chain fatty acids in the human colon: relation to gastrointestinal health and disease. Scandinavian journal of gastroenterology. Supplement, 216, 132–148. https://doi.org/10.3109/00365529609094568

Murray, R. L., Zhang, W., Iwaniuk, M., Grilli, E., & Stahl, C. H. (2018). Dietary tributyrin, an HDAC inhibitor, promotes muscle growth through enhanced terminal differentiation of satellite cells. Physiological reports, 6(10), e13706. https://doi.org/10.14814/phy2.13706

Ohira H, Fujioka Y, Katagiri C, Mamoto R, Aoyama-Ishikawa M, Amako K, Izumi Y, Nishiumi S, Yoshida M, Usami M, Ikeda M. Butyrate attenuates inflammation and lipolysis generated by the interaction of adipocytes and macrophages. J Atheroscler Thromb. 2013;20(5):425-42.

Roberto Berni Canani, Margherita Di Costanzo and Ludovica Leone. The epigenetic effects of butyrate: potential therapeutic implications for clinical practice. Clinical Epigenetics 2012, 4:4. http://www.clinicalepigeneticsjournal.com/content/4/1/4

Scheppach W. (1994). Effects of short chain fatty acids on gut morphology and function. Gut, 35(1 Suppl), S35–S38. https://doi.org/10.1136/gut.35.1_suppl.s35

Singh, N., Thangaraju, M., Prasad, P,D., Martin, P,M., Lambert, N,A., Boettger, T., Offermanns, S., Ganapathy, V. (2010) Blockade of Dendritic Cell Development by Bacterial Fermentation Products Butyrate and Propionate through a Transporter (Slc5a8)-dependent Inhibition of Histone Deacetylases. The Journal of Biological Chemistry. Sept 2010. 285: 36 (27601-27609). http://www.jbc.org/content/285/36/27601.full.pdf

Tazoe, H., Otomo, Y., Kaji, I., Tanaka, R., Karaki, S. I., & Kuwahara, A. (2008). Roles of short-chain fatty acids receptors, GPR41 and GPR43 on colonic functions. Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 59 Suppl 2, 251–262.

Wang, C., Cao, S., Zhang, Q., Shen, Z., Feng, J., Hong, Q., Lu, J., Xie, F., Peng, Y., & Hu, C. (2019). Dietary Tributyrin Attenuates Intestinal Inflammation, Enhances Mitochondrial Function, and Induces Mitophagy in Piglets Challenged with Diquat. Journal of agricultural and food chemistry, 67(5), 1409–1417. https://doi.org/10.1021/acs.jafc.8b06208

Wang, C., Cao, S., Shen, Z., Hong, Q., Feng, J., Peng, Y., & Hu, C. (2019). Effects of dietary tributyrin on intestinal mucosa development, mitochondrial function and AMPK-mTOR pathway in weaned pigs. Journal of animal science and biotechnology, 10, 93. https://doi.org/10.1186/s40104-019-0394-x

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