Efficacy of sodium butyrate adjunct therapy in shigellosis: a randomized, double-blind, placebo-controlled clinical trial

BMC Infectious Diseases

Research Article

Jan Andersson¹  Birgitta Agerberth²  Gudmundur H Gudmundsson³  Akhirunnesa Mily⁴  Nur Haque Alam⁴  Alejandro Cravioto⁴  Abu Saleh Mohammed Arifuzzaman⁴  Protim Sarker⁵  Rokeya Sultana Rekha⁵  Rubhana Raqib⁶ 

[1] Center for Infectious Medicine, Department of Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden;Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden;Institute of Biology, University of Iceland, Reykjavik, Iceland;International Centre for Diarrheal Disease Research, Dhaka, Bangladesh;International Centre for Diarrheal Disease Research, Dhaka, Bangladesh;Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden;International Centre for Diarrheal Disease Research, Dhaka, Bangladesh;Nutritional Biochemistry Laboratory, Laboratory Sciences Division, International Centre for Diarrheal Disease Research, Bangladesh (icddr,b), 1212, Mohakhali, Dhaka, Bangladesh;

关键词: Short chain fatty acids;    Butyrate;    Shigellosis;    Innate immunity;    Antimicrobial peptides;    Cathelicidin;    LL-37;    Inflammation;    Pro-inflammatory cytokines;    Rectal mucosa;   

DOI  :  10.1186/1471-2334-12-111

 received in 2011-12-15, accepted in 2012-05-02,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundTreatment 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.MethodsA 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.ResultsCompared 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.ConclusionAdjunct 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.Trial RegistrationClinicalTrials.gov, NCT00800930.

【 授权许可】

CC BY   
© Raqib et al.; licensee BioMed Central Ltd. 2012