Chemistry:Tributyrin

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Tributyrin, also known as glyceryl tributyrate, is a triglyceride (fat) naturally present in butter.[1][2][3] It is an ester composed of three butyric acid (butyrate) moieties and glycerol.[4] It can be described as a liquid fat with an acrid taste. About 3 to 4% of butter is tributyrin, with butter being the richest known food source of tributyrin.[2] It is a slowly converted precursor or prodrug of the short-chain fatty acid (SCFA) butyric acid, which is a major product of gut bacteria and hence "postbiotic".[5]

Pharmacology

Tributyrin is a precursor or prodrug of the endogenous short-chain fatty acid (SCFA) butyric acid (butyrate).[3][1] It is stable and is rapidly absorbed and gradually converted into butyric acid.[1] Tributyrin is not broken down by gastric juice and is slowly converted into butyric acid and glycerol by pancreatic lipases in the gut.[6] In addition, tributyrin is more lipophilic than butyric acid and is taken up into cells much more readily in comparison.[3] Butyric acid itself has an extremely short elimination half-life of seconds to minutes among other limitations, which makes its own use impractical.[1]

Butyric acid, the active form of tributyrin, has a large variety of biological effects.[5] It is an agonist of the FFAR2 (GPR43), FFAR3 (GPR41), and GPR109A and a histone deacetylase (HDAC) inhibitor of HDAC classes I and II.[5] In addition, butyric acid is the preferred energy source for colonocytes, and has been found to provide approximately 70% of total energy needs for colonocytes in mice.[5] Butyrate plays a key role in gut homeostasis and has anti-inflammatory effects among others.[5] Tributyrin is described as an HDAC inhibitor similarly to butyric acid.[7][8]

Tributyrin has been found to reverse gut microbiota dysbiosis and intestinal injury and inflammation induced by antibiotics in rodents.[3][6] This included increasing potentially beneficial SCFA-producing bacteria such as Muribaculaceae and Bifidobacterium and decreasing potentially pathogenic bacteria such as Bacteroidetes and Enterococcus.[6] One means by which SCFAs like butyrate may mediate such effects is by decreasing intestinal pH.[9] In accordance with the observed intestinal bacterial changes, tributyrin increased levels of the SFCAs butyric acid, acetic acid (acetate), and propionic acid (propionate).[6] The effects of tributyrin and butyrate appear to be dose-dependent, with low concentrations promoting the intestinal barrier and inhibiting inflammation while high concentrations can do the opposite via induction of apoptosis.[3][6] In addition to reversing antibiotic-induced dysbiosis, tributyrin has been found to strongly reduce Clostridium difficile infection in rodents.[3][10] Coadministration of tributyrin with the probiotics Limosilactobacillus reuteri and Lacticaseibacillus rhamnosus has been found to synergistically increase butyrate levels in humans ex vivo as well.[11][12]

In vitro, butyric acid is known to activate the brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) signaling pathway via its HDAC inhibition.[13]

Other uses

Tributyrin is used in microbiological laboratories to identify the bacterium Moraxella catarrhalis.[14]

Research

Tributyrin was under formal clinical development for the treatment of solid tumors in the late 1990s, but no further development was subsequently reported.[15]

See also

References

  1. ↑ 1.0 1.1 1.2 1.3 "Anticarcinogenic actions of tributyrin, a butyric acid prodrug". Curr Drug Targets 13 (14): 1720–1729. December 2012. doi:10.2174/138945012804545443. PMID 23140283. 
  2. ↑ 2.0 2.1 "Rationale for the luminal provision of butyrate in intestinal diseases". Eur J Nutr 39 (4): 164–171. August 2000. doi:10.1007/s003940070020. PMID 11079736. "A direct source of butyrate is the diet, where it is present at low levels in many fruits and vegetables, but its richest source is from milk fat (butter) which contains 3–4 % butyrate as glycerol esters, termed tributyrin". 
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 "Gut microbiota-derived short-chain fatty acids (SCFAs): immunomodulatory effects and therapeutic potential in infections". Clin Microbiol Rev: e0036825. June 2026. doi:10.1128/cmr.00368-25. PMID 42267834. 
  4. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named Merck
  5. ↑ 5.0 5.1 5.2 5.3 5.4 "Gut microbiota-derived short-chain fatty acids and their role in human health and disease". Nat Rev Microbiol 23 (10): 635–651. October 2025. doi:10.1038/s41579-025-01183-w. PMID 40360779. 
  6. ↑ 6.0 6.1 6.2 6.3 6.4 "Tributyrin alleviates gut microbiota dysbiosis to repair intestinal damage in antibiotic-treated mice". PLoS One 18 (7). 2023. doi:10.1371/journal.pone.0289364. PMID 37523400. Bibcode: 2023PLoSO..1889364Y. 
  7. ↑ "p21Waf1/Cip1 is a common target induced by short-chain fatty acid HDAC inhibitors (valproic acid, tributyrin and sodium butyrate) in neuroblastoma cells". Oncol Rep 13 (6): 1139–1144. June 2005. PMID 15870934. 
  8. ↑ "Butyric acid and prospects for creation of new medicines based on its derivatives: a literature review". J Vet Sci 25 (2). March 2024. doi:10.4142/jvs.23230. PMID 38568825. 
  9. ↑ "Unlocking the power of postbiotics: A revolutionary approach to nutrition for humans and animals". Cell Metab 36 (4): 725–744. April 2024. doi:10.1016/j.cmet.2024.03.004. PMID 38569470. 
  10. ↑ "The role of short-chain fatty acids in Clostridioides difficile infection: A review". Anaerobe 75. June 2022. doi:10.1016/j.anaerobe.2022.102585. PMID 35545183. 
  11. ↑ "Lactobacillus rhamnosus: An emerging probiotic with therapeutic potential for depression". Pharmacol Res 211. January 2025. doi:10.1016/j.phrs.2024.107541. PMID 39653301. "Supplementation with tributyrin (TB) significantly raises butyrate levels, and L. rhamnosus ATCC 53103 (LGG) may enhance butyrate production by modulating the gut microbiota [117].". 
  12. ↑ "Lacticaseibacillus rhamnosus ATCC 53103 and Limosilactobacillus reuteri ATCC 53608 Synergistically Boost Butyrate Levels upon Tributyrin Administration Ex Vivo". Int J Mol Sci 24 (6): 5859. March 2023. doi:10.3390/ijms24065859. PMID 36982942. 
  13. ↑ "From gut to glee: Is butyrate a promising antidepressant? A systematic review and mechanistic insights". Brain Behav Immun 132. February 2026. doi:10.1016/j.bbi.2025.106237. PMID 41429215. 
  14. ↑ Pérez, José L.; Pulido, Angeles; Pantozzi, Florencia; Martin, Rogelio (October 1990). "Butyrate esterase (4-methylumbelliferyl butyrate) spot test, a simple method for immediate identification of Moraxella (Branhamella) catarrhalis corrected". Journal of Clinical Microbiology (Washington, DC: American Society for Microbiology) 28 (10): 2347–2348. doi:10.1128/jcm.28.10.2347-2348.1990. ISSN 1098-660X. PMID 2121784. 
  15. ↑ "Tributyrin". 23 September 2021. https://adisinsight.springer.com/drugs/800010141. 



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