Berberine blocks the relapse of Clostridium difficile infection in C57BL/6 mice after standard vancomycin treatment.

Abstract

Vancomycin is a preferred antibiotic for treating Clostridium difficile infection (CDI) and has been associated with a rate of recurrence of CDI of as high as 20% in treated patients. Recent studies have suggested that berberine, an alternative medical therapy for gastroenteritis and diarrhea, exhibits several beneficial effects, including induction of anti-inflammatory responses and restoration of the intestinal barrier function. This study investigated the therapeutic effects of berberine on preventing CDI relapse and restoring the gut microbiota in a mouse model. Berberine was administered through gavage to C57BL/6 mice with established CDI-induced intestinal injury and colitis. The disease activity index (DAI), mean relative weight, histopathology scores, and levels of toxins A and B in fecal samples were measured. An Illumina sequencing-based analysis of 16S rRNA genes was used to determine the overall structural change in the microbiota in the mouse ileocecum. Berberine administration significantly promoted the restoration of the intestinal microbiota by inhibiting the expansion of members of the family Enterobacteriaceae and counteracting the side effects of vancomycin treatment. Therapy consisting of vancomycin and berberine combined prevented weight loss, improved the DAI and the histopathology scores, and effectively decreased the mortality rate. Berberine prevented CDIs from relapsing and significantly improved survival in the mouse model of CDI. Our data indicate that a combination of berberine and vancomycin is more effective than vancomycin alone for treating CDI. One of the possible mechanisms by which berberine prevents a CDI relapse is through modulation of the gut microbiota. Although this conclusion was generated in the case of the mouse model, use of the combination of vancomycin and berberine and represent a novel therapeutic approach targeting CDI.

• Authors: Zhi Lv, Guoli Peng, Weihua Liu, Hufeng Xu, JianRong Su
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 59 Issue 7 Pg. 3726-35 (Jul 2015) ISSN: 1098-6596 [Electronic] United States
• PMID: 25824219 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Chemical References

• Anti-Bacterial Agents
• Bacterial Proteins
• Bacterial Toxins
• DNA, Bacterial
• Enterotoxins
• RNA, Ribosomal, 16S
• tcdA protein, Clostridium difficile
• toxB protein, Clostridium difficile
• Berberine
• Vancomycin

Topics

• Animals
• Anti-Bacterial Agents (therapeutic use)
• Bacterial Proteins (analysis)
• Bacterial Toxins (analysis)
• Base Sequence
• Berberine (therapeutic use)
• Clostridioides difficile (drug effects)
• Colitis (microbiology, pathology)
• DNA, Bacterial (genetics)
• Disease Models, Animal
• Drug Therapy, Combination
• Enterobacteriaceae (drug effects)
• Enterocolitis, Pseudomembranous (drug therapy, microbiology, prevention & control)
• Enterotoxins (analysis)
• Feces (microbiology)
• Gastrointestinal Microbiome (drug effects, genetics)
• Mice
• Mice, Inbred C57BL
• RNA, Ribosomal, 16S (genetics)
• Random Allocation
• Recurrence
• Sequence Analysis, DNA
• Vancomycin (adverse effects, therapeutic use)
• Weight Loss (drug effects)