title: Efficacy of sodium butyrate adjunct therapy in shigellosis: a randomized, double-blind, placebo-controlled clinical trial.
abstract: BACKGROUND
  Treatment of shigellosis in rabbits with butyrate reduces clinical severity and counteracts the downregulation of cathelicidin (CAP-18) in the large intestinal epithelia. Here, we aimed to evaluate whether butyrate can be used as an adjunct to antibiotics in the treatment of shigellosis in patients.
  
  
  METHODS
  A randomized, double-blind, placebo-controlled, parallel-group designed clinical trial was conducted. Eighty adult patients with shigellosis were randomized to either the Intervention group (butyrate, n = 40) or the Placebo group (normal saline, n = 40). The Intervention group was given an enema containing sodium butyrate (80 mM), twice daily for 3 days, while the Placebo group received the same dose of normal saline. The primary endpoint of the trial was to assess the efficacy of butyrate in improving clinical, endoscopic and histological features of shigellosis. The secondary endpoint was to study the effect of butyrate on the induction of antimicrobial peptides in the rectum. Clinical outcomes were assessed and concentrations of antimicrobial peptides (LL-37, human beta defensin1 [HBD-1] and human beta defensin 3 [HBD-3]) and pro-inflammatory cytokines (interleukin-1β [IL-1β] and interleukin-8 [IL-8]) were measured in the stool. Sigmoidoscopic and histopathological analyses, and immunostaining of LL-37 in the rectal mucosa were performed in a subgroup of patients.
  
  
  RESULTS
  Compared with placebo, butyrate therapy led to the early reduction of macrophages, pus cells, IL-8 and IL-1β in the stool and improvement in rectal histopathology. Butyrate treatment induced LL-37 expression in the rectal epithelia. Stool concentration of LL-37 remained significantly higher in the Intervention group on days 4 and 7.
  
  
  CONCLUSIONS
  Adjunct therapy with butyrate during shigellosis led to early reduction of inflammation and enhanced LL-37 expression in the rectal epithelia with prolonged release of LL-37 in the stool.
  
  
  BACKGROUND
  ClinicalTrials.gov, NCT00800930.
authors.affiliation: International Centre for Diarrheal Disease Research, Dhaka, Bangladesh. rubhana@icddrb.org
authors.forename: Rubhana
authors.initials: R
authors.lastname: Raqib
authors.forename: Protim
authors.initials: P
authors.lastname: Sarker
authors.forename: Akhirunnesa
authors.initials: A
authors.lastname: Mily
authors.forename: Nur Haque
authors.initials: NH
authors.lastname: Alam
authors.forename: Abu Saleh Mohammed
authors.initials: AS
authors.lastname: Arifuzzaman
authors.forename: Rokeya Sultana
authors.initials: RS
authors.lastname: Rekha
authors.forename: Jan
authors.initials: J
authors.lastname: Andersson
authors.forename: Gudmundur H
authors.initials: GH
authors.lastname: Gudmundsson
authors.forename: Alejandro
authors.initials: A
authors.lastname: Cravioto
authors.forename: Birgitta
authors.initials: B
authors.lastname: Agerberth
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D002087:Butyrates / Q000008:administration & dosage*; D015510:Clinical Medicine / Q000379:methods; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000379:methods; D004405:Dysentery, Bacillary / Q000188:drug therapy* / Q000473:pathology; D004724:Endoscopy; D005243:Feces / Q000737:chemistry; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D011817:Rabbits; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D002087:Butyrates; D010919:Placebos