Tributyrin supplementation protects mice from acute ethanol-induced gut injury

Alcohol Clin Exp Res. 2014 Jun;38(6):1489-501. doi: 10.1111/acer.12428. Epub 2014 May 30.


Background: Excessive alcohol consumption leads to liver disease. Interorgan crosstalk contributes to ethanol (EtOH)-induced liver injury. EtOH exposure causes gut dysbiosis resulting in negative alterations in intestinal fermentation byproducts, particularly decreased luminal butyrate concentrations. Therefore, in the present work, we investigated the effect of butyrate supplementation, in the form of trybutyrin, as a prophylactic treatment against EtOH-induced gut injury.

Methods: C57BL/6J mice were treated with 3 different EtOH feeding protocols: chronic feeding (25 days, 32% of kcal), short-term (2 days, 32%), or acute single gavage (5 g/kg). Tributyrin (0.83 to 10 mM) was supplemented either into the liquid diet or by oral gavage. Intestinal expression of tight junction (TJ) proteins and a butyrate receptor and transporter were evaluated, as well as liver enzymes and inflammatory markers.

Results: All 3 EtOH exposure protocols reduced the expression and co-localization of TJ proteins (ZO-1, occludin) and the expression of a butyrate receptor (GPR109A) and transporter (SLC5A8) in the ileum and proximal colon. Importantly, tributyrin supplementation protected against these effects. Protection of the intestine with tributyrin supplementation was accompanied by mitigation of EtOH-induced increases in aspartate aminotransferase and inflammatory measures in the short-term and acute EtOH exposure protocols, but not after chronic EtOH feeding.

Conclusions: These findings suggest that tributyrin supplementation could serve as a prophylactic treatment against gut injury caused by short-term EtOH exposure.

Keywords: Butyrate; Ethanol; Intestine; Liver; Tributyrin.

MeSH terms

  • Alanine Transaminase / analysis
  • Animals
  • Colon / chemistry
  • Colon / drug effects
  • Dietary Supplements
  • Digestive System Diseases / chemically induced*
  • Digestive System Diseases / prevention & control
  • Dysbiosis / chemically induced
  • Dysbiosis / prevention & control
  • Ethanol / adverse effects*
  • Ethanol / antagonists & inhibitors
  • Fatty Liver / chemically induced
  • Fatty Liver / prevention & control
  • Female
  • Ileum / chemistry
  • Ileum / drug effects
  • Liver / chemistry
  • Liver / drug effects
  • Liver / pathology
  • Mice
  • Mice, Inbred C57BL
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tight Junction Proteins / analysis
  • Tight Junction Proteins / metabolism
  • Triglycerides / analysis
  • Triglycerides / therapeutic use*


  • Tight Junction Proteins
  • Triglycerides
  • Ethanol
  • Alanine Transaminase
  • tributyrin