Butyrate

Butyric acid from the Greek βουτυρος (butter) is a short-chain fatty acid (SCFA) with four carbon atoms. It is found in vegetable oils and animal fats. Butyric acid has an unpleasant smell and a bitter and pungent taste.

Butyrate is the traditional name for the conjugated base of butyric acid. The name is used in the name of esters such as butyrate monoglyceride and butyric acid salts (sodium butyrate).

Butyrate is the main source of energy for epithelial cells (colonocytes).

Where can I find butyrate? What foods contain butyrate?

Butyrate is found in butter and ghee as tributyrin. Butter can contain 3-5% tributyrin.

Butyrate is obtained during the fermentation of dietary fibre by the microbiota.

Butyrate: a key metabolite of the microbiota

The bacteria that colonize the digestive tract, especially the colon, consume the prebiotics we consume to be able to reproduce. Prebiotics are food substances generally composed of bound sugars (oligosaccharides and polysaccharides). Prebioticas are essential to the intestinal microbiota.

Indeed, these fibres are transformed by the microbiota into short-chain fatty acids (SCFAs). Among them, butyrate plays a crucial role in intestinal physiology, as it is one of the preferred sources of carbon in colon epithelial cells. Without butyrate, these cells would be in energy “deficiency.

Biological roles of butyrate

First, SCFAs have effects on the gastrointestinal tract and ensure proper intestinal function. Their primary function is to serve as an energy source for the cells in the colon. Butyrate is the main source of energy for colonocytes, or the cells that form the colon wall. It allows them to multiply and function normally. Without these compounds, these cells undergo autophagy and eventually enter apoptosis, and die.

Butyrate has an anti-inflammatory action, acts on intestinal motility (constipation and diarrhoea), and stimulates the absorption of water and sodium. Also, it improves dysbiosis, i.e, the gut microbiota balance and contributes to protecting the mucus layer of the intestine. (Canani 2011)

Benefits of butyrate

 

Application

Benefits (Manrique 2017)

Inflammation of the intestine

Trophic and anti-inflammatory action

Coeliacs

Trophic action on the intestinal epithelium

Restores microbiotic balance

Irritable bowel syndrome (IBS)

Regulates intestinal motility

Restores the balance of the intestinal microbiota

Constipation

Regulates intestinal motility

Restores the balance of the intestinal microbiota

Diarrhoea related to antibiotics

Restores the balance of the intestinal microbiota

Taking deleterious drugs on the intestinal epithelium

(chemotherapy, anti-inflammatory drugs, etc.)

Trophic action on the intestinal epithelium

Restores microbiotic balance

Clinical studies with butyrate

Crohn’s disease

Thirteen patients with Crohn’s disease received 4 g/day of butyrate as enteric-coated tablets for 8 weeks. A colonoscopy with ileoscopy was performed before and after the treatment. Butyrate intake was well tolerated and resulted in improvements. Of the nine patients (69%) who responded to treatment, seven (53%) had a remission, and two had a partial response. (Di Sabatino 2015)

Ulcer colitis

In Italy, an open-label study was conducted by 19 gastrointestinal units (GISDI study group) in 216 patients with ulcer colitis who had an incomplete response to standard therapy (mesalazine). In this study, in addition to the standard treatment (mesalazine 3 x 800 mg/d), patients took three times daily one intestinal absorption resistant tablet containing (300 mg butyrate and 250 mg inulin). The investigators reported a significant improvement in the symptoms and appearance of mucous membranes. (Assisi 2008)

Irritable Bowel Syndrome (IBS)

In irritable bowel syndrome, 66 patients who received 300 mg butyric acid (oral) for 12 weeks showed a significant decrease compared to placebo in abdominal pain during defecation after 4 weeks. A reduction in the incidence of constipation was demonstrated in the control group in a statistically significant manner at 12 weeks. (Banasiewicz 2013)

Diverticulosis

Finally, oral supplementation with microencapsulated butyric acid (300mg/day) was evaluated to reduce the incidence of diverticulitis in people with diverticulose. 73 patients participated in this randomized, placebo-controlled study. At 12 months, the treated group noted a significant decrease in the number of diverticulitis episodes compared to the control group. (Krokowicz 2014)

It should be noted that in all these studies, the administration of the different forms of butyric acid had no adverse effects and was well tolerated.

Clinical studies with tributyrin

Tributyrin is currently attracting increasing interest as a source of butyric acid (butyrate). In clinical pharmacological studies, it has been shown to be a well-tolerated form. (Edelman 2003)

Tributyrin has been used until now in enteral nutrition in combination with other nutrients. Several studies with tributyrin-containing formulations have been conducted in critically ill patients under enteral nutritional assistance (Scheppach 2003; Beale 2008). The dose used in these trials was generally 1 gram of tributyrin per day. The results include a decrease in constipation and an improvement in gastrointestinal tolerance.

Watch our webinar on Short-Chains Fatty Acids and gut microbiota

Butyrate food supplement

Tributyrin provides 3 molecules of butyrate. It is the short-chain fatty acid found in butter.

It is an interesting form to take as a dietary supplement of butyrate. Unlike butyrate, it does not have an unpleasant smell.

In addition, the microencapsulated tributyrin in Butycaps is more effective than butyrate salts (sodium butyrate) for the digestion, bioavailability and activity of butyrate in the colon.

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Assisi RF; GISDI Study Group. Combined butyric acid/mesalazine treatment in ulcerative colitis with mild-moderate activity. Minerva Gastroenterol Dietol 2008;54(3):231-8.

Banasiewicz T, Krokowicz Ł, Stojcev Z, Kaczmarek BF, Kaczmarek E, Maik J, et al. Microencapsulated sodium butyrate reduces the frequency of abdominal pain in patients with irritable bowel syndrome. Colorectal Dis 2013;15(2):204-9.

Beale RJ, Sherry T, Lei K, Campbell-Stephen L, McCook J, Smith J, et al. Early enteral supplementation with key pharmaconutrients improves Sequential Organ Failure Assessment score in critically ill patients with sepsis: outcome of a randomized, controlled, double-blind trial. Crit Care Med 2008;36(1):131-44.

Canani RB, Costanzo MD, Leone L, Pedata M, Meli R, Calignano A. Potential beneficial effects of butyrate in intestinal and extraintestinal diseases. World J Gastroenterol. 2011 28;17(12):1519-28.

Edelman MJ, Bauer K, Khanwani S, Tait N, Trepel J, Karp J, et al. Clinical and pharmacologic study of tributyrin: an oral butyrate prodrug. Cancer Chemother Pharmacol 2003; 51(5):439-44.

Di Sabatino A, Morera R, Ciccocioppo R, Cazzola P, Gotti S, Tinozzi FP, et al. Oral butyrate for mildly to moderately active Crohn’s disease. Aliment Pharmacol Ther 2005;22(9):789-94.

Koh A, De Vadder F, Kovatcheva-Datchary P, Bäckhed F. From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites. Cell. 2016 Jun 2;165(6):1332-1345. 

Krokowicz L, Stojcev Z, Kaczmarek BF, Kociemba W, Kaczmarek E, Walkowiak J, et al. Microencapsulated sodium butyrate administered to patients with diverticulosis decreases incidence of diverticulitis-a prospective randomized study. Int J Colorectal Dis 2014;29(3):387-93.

Manrique Vergara D., González Sánchez M.E. Short chain fatty acids (butyric acid) and intestinal diseases. Nutr Hosp 2017; 34(Supl. 4):58-6.

Papillon E, Bonaz B, Fournet J. [Short chain fatty acids: effects on gastrointestinal function and therapeutic potential in gastroenterology]. Gastroenterol Clin Biol. 1999 Jun-Jul;23(6-7):761-9. Review. 

Scheppach WM. Intestamin and acute pancreatitis. Clin Nutr 2003;22(Supp. 1):32.