Sodium butyrate supplementation ameliorates diabetic inflammation in db/db mice

J Endocrinol. 2018 Sep;238(3):231-244. doi: 10.1530/JOE-18-0137. Epub 2018 Jun 25.


Endotoxemia has been recognized to be closely accompanied with type 2 diabetes mellitus (T2DM) and is responsible for many diabetic complications. Recent study suggests the potential role of butyrate, a short-chain fatty acid (SCFA) from microbiota metabolite, on T2DM. Gut-leak is a key event in diabetic-endotoxemia. To investigate if butyrate could ameliorate diabetic-endotoxemia, both in vivo and in vitro experiments were carried out in the present study. The effect of butyrate supplementation on blood HbA1c and inflammatory cytokines were determined in db/db mice; gut barrier integrity and expression of tight junction proteins were investigated both in vivo and in vitro Oral butyrate administration significantly decreased blood HbA1c, inflammatory cytokines and LPS in db/db mice; inflammatory cell infiltration was reduced, and gut integrity and intercellular adhesion molecules were increased as detected by HE staining, immunohistochemistry and Western blot. By gut microbiota assay, ratio of Firmicutes:Bacteroidetes for gut microbiota was reduced by butyrate. In Caco-2 cells, butyrate significantly promoted cell proliferation, decreased inflammatory cytokines' secretion, enhanced cell anti-oxidative stress ability and preserved the epithelial monocellular integrity, which was damaged by LPS. The present findings demonstrated that butyrate supplementation could ameliorate diabetic-endotoxemia in db/db mice via restoring composition of gut microbiota and preserving gut epithelial barrier integrity.

Keywords: butyrate; endotoxemia; gut barrier; inflammation; type 2 diabetes mellitus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Butyric Acid / administration & dosage*
  • Caco-2 Cells
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy
  • Drug Therapy, Combination
  • Gastrointestinal Microbiome / drug effects
  • Humans
  • Inflammation / etiology
  • Inflammation / prevention & control*
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / microbiology
  • Intestinal Mucosa / physiology
  • Male
  • Metformin / administration & dosage
  • Mice
  • Mice, Inbred C57BL


  • Butyric Acid
  • Metformin