title: 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.affiliation: Clinical Laboratory Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Lv
authors.affiliation: Clinical Laboratory, Beijing Gong An Hospital, Beijing, China.
authors.forename: Guoli
authors.initials: G
authors.lastname: Peng
authors.affiliation: Department of Pathology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Liu
authors.affiliation: Animal Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Hufeng
authors.initials: H
authors.lastname: Xu
authors.affiliation: Clinical Laboratory Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China friendshiplab@sina.com.
authors.forename: JianRong
authors.initials: J
authors.lastname: Su
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000032:analysis; D001427:Bacterial Toxins / Q000032:analysis; D001483:Base Sequence; D001599:Berberine / Q000627:therapeutic use*; D016360:Clostridioides difficile / Q000187:drug effects; D003092:Colitis / Q000382:microbiology / Q000473:pathology; D004269:DNA, Bacterial / Q000235:genetics; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004755:Enterobacteriaceae / Q000187:drug effects; D004761:Enterocolitis, Pseudomembranous / Q000188:drug therapy* / Q000382:microbiology / Q000517:prevention & control; D004768:Enterotoxins / Q000032:analysis; D005243:Feces / Q000382:microbiology; D000069196:Gastrointestinal Microbiome / Q000187:drug effects* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D011897:Random Allocation; D012008:Recurrence; D017422:Sequence Analysis, DNA; D014640:Vancomycin / Q000009:adverse effects / Q000627:therapeutic use*; D015431:Weight Loss / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004269:DNA, Bacterial; D004768:Enterotoxins; D012336:RNA, Ribosomal, 16S; C041348:tcdA protein, Clostridium difficile; C031815:toxB protein, Clostridium difficile; D001599:Berberine; D014640:Vancomycin
references.citation: J Pharmacol Exp Ther. 2000 Sep;294(3):822-9
references.pmid: 10945829
references.citation: Proc Natl Acad Sci U S A. 2011 Mar 15;108 Suppl 1:4639-44
references.pmid: 20616009
references.citation: Arch Pathol Lab Med. 1983 Apr;107(4):211-3
references.pmid: 6687545
references.citation: Zhongguo Zhong Xi Yi Jie He Za Zhi. 1994 Dec;14(12):718-20
references.pmid: 7719104
references.citation: Clin Infect Dis. 1997 Sep;25(3):729-32
references.pmid: 9314469
references.citation: Infect Control Hosp Epidemiol. 1999 Jan;20(1):43-50
references.pmid: 9927265
references.citation: Inflamm Bowel Dis. 2005 May;11(5):455-63
references.pmid: 15867585
references.citation: Antimicrob Agents Chemother. 2008 Mar;52(3):1121-6
references.pmid: 18195066
references.citation: Biochemistry. 2008 Mar 11;47(10):3225-34
references.pmid: 18275156
references.citation: Phytother Res. 2008 Aug;22(8):999-1012
references.pmid: 18618524
references.citation: Infect Immun. 2008 Oct;76(10):4726-36
references.pmid: 18678663
references.citation: Gastroenterology. 2008 Dec;135(6):1984-92
references.pmid: 18848941
references.citation: Nat Methods. 2010 May;7(5):335-6
references.pmid: 20383131
references.citation: Cold Spring Harb Protoc. 2010 Jun;2010(6):pdb.prot5448
references.pmid: 20516186
references.citation: Infect Immun. 2011 Jul;79(7):2856-64
references.pmid: 21576341
references.citation: Med Sci Monit. 2011 Jul;17(7):RA164-7
references.pmid: 21709646
references.citation: Gut Microbes. 2011 May-Jun;2(3):145-58
references.pmid: 21804357
references.citation: Clin Infect Dis. 2011 Nov;53(10):994-1002
references.pmid: 22002980
references.citation: Curr Opin Gastroenterol. 2012 Jan;28(1):1-9
references.pmid: 22134217
references.citation: Am J Physiol Gastrointest Liver Physiol. 2012 Mar 1;302(5):G504-14
references.pmid: 22173918
references.citation: Nucleic Acids Res. 2013 Jan;41(Database issue):D590-6
references.pmid: 23193283
references.citation: Infect Immun. 1982 Feb;35(2):471-5
references.pmid: 7035365
references.citation: J Bacteriol. 2010 Oct;192(19):4983-90
references.pmid: 20675492
references.citation: J Bacteriol. 2011 Jan;193(1):274-82
references.pmid: 20971909
references.citation: J Infect Dis. 2013 May 15;207(10):1498-504
references.pmid: 23420906