Beneficial effects of butyrate in intestinal injury

Purpose: Butyrate is a short-chain fatty acid produced in the intestine. It is controversial whether butyrate is protective or destructive for the intestinal epithelium in the development of diseases like necrotizing enterocolitis (NEC), and its mechanism of action remains unclear. We aimed to determine the effect of butyrate on the intestinal epithelium by studying its effects on intestinal epithelial cells (IEC-18) exposed to injury and in vivo by investigating the effects on the intestine in an experimental model of NEC.

Methods: A) In vitro study: Butyrate was given to normal IEC-18 to determine the dose triggering injury. Based on above results, low dose butyrate (1 mM) was given to H₂O₂-injured cells to determine its effect against inflammation. B) In vivo study: NEC was induced by hypoxia and gavage feeding between postnatal day P5 and P9 (n = 8). Breastfed mice were used as control (n = 7). Butyrate (150 mM) was administered by enema on P6 in NEC (n = 6). Distal ileum was harvested on P9.

Results: High dose (16 mM) butyrate upregulated inflammatory marker IL-6, while low dose butyrate protected cells from injury by reducing IL-6 expression. Similarly, compared with NEC alone, NEC mice who received butyrate had reduced intestinal damage, reduced IL-6 and NF-ĸB expression, and increased intestinal tight junction marker Claudin-7.

Conclusion: Butyrate has opposite effects depending on the dose administered. Butyrate can protect cells from H₂O₂-induced injury and can in vivo protect the intestine from NEC. This beneficial effect is because of downregulation of inflammation and enhancement of intestinal barrier.