Effect of butyrate enemas on gene expression profiles and endoscopic/histopathological scores of diverted colorectal mucosa: A randomized trial

Dig Liver Dis. 2016 Jan;48(1):27-33. doi: 10.1016/j.dld.2015.09.005. Epub 2015 Sep 28.

Abstract

Background: A temporary stoma is often created to protect a distal anastomosis in colorectal surgery. Short-chain fatty acids, mainly butyrate, are the major fuel source for the epithelium and their absence in the diverted tract may produce mucosal atrophy and inflammation.

Aims: To investigate whether the administration of sodium butyrate enemas (Naburen(©), Promefarm, Italy) could prevent mucosal inflammation and atrophy and affect gene expression profiles after ileo/colostomy.

Methods: We performed a randomized, double-blind, placebo-controlled clinical trial, in patients with enterostomy performed for inflammatory bowel disease, colorectal cancer or diverticulitis. Twenty patients were randomly allocated to receive 30ml of sodium butyrate 600mmol/L (group A) or saline (group B), b.i.d. for 30 days.

Results: In group A endoscopic scores were significantly improved (p<0.01) while mucosal atrophy was reduced or unchanged; in group B mucosal atrophy was increased in 42.8% of patients. Despite the high dose of butyrate used, no short-chain fatty acids were detectable by gas chromatography-mass spectrometry in colorectal biopsies. Group A patients showed up-regulation of genes associated with mucosal repair such as Wnt signalling, cytoskeleton regulation and bone morphogenetic protein-antagonists.

Conclusion: Butyrate enemas may prevent the atrophy of the diverted colon/rectum, thus improving the recovery of tissue integrity.

Keywords: Bone morphogenetic protein (BMP) antagonists; Diversion colitis; Gene expression profiles; Inflammatory bowel disease; Topic butyrate.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adult
  • Aged
  • Atrophy / etiology
  • Atrophy / pathology
  • Atrophy / prevention & control
  • Butyric Acid / administration & dosage
  • Butyric Acid / pharmacology*
  • Colitis / etiology
  • Colitis / pathology
  • Colitis / prevention & control
  • Colon / drug effects
  • Colon / pathology
  • Colonoscopy
  • Colostomy / adverse effects
  • Cytokines
  • Double-Blind Method
  • Enema
  • Fatty Acids, Volatile / analysis
  • Female
  • Gastrointestinal Agents / administration & dosage
  • Gastrointestinal Agents / pharmacology*
  • Gene Expression / drug effects*
  • Humans
  • Ileostomy / adverse effects
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intestinal Mucosa / chemistry
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / pathology*
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Middle Aged
  • Proctitis / etiology
  • Proctitis / pathology
  • Proctitis / prevention & control
  • Proteins / genetics
  • Rectum / drug effects
  • Rectum / pathology
  • Transcriptome / drug effects
  • Wnt Signaling Pathway / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • Cytokines
  • Fatty Acids, Volatile
  • GREM2 protein, human
  • Gastrointestinal Agents
  • Intercellular Signaling Peptides and Proteins
  • Intracellular Signaling Peptides and Proteins
  • Proteins
  • SOSTDC1 protein, human
  • Butyric Acid