Rifaximin modulates the colonic microbiota of patients with Crohn's disease: an in vitro approach using a continuous culture colonic model system.
OBJECTIVE
Rifaximin, a rifamycin derivative, has been reported to induce clinical remission of active Crohn's disease (CD), a chronic inflammatory bowel disorder. In order to understand how rifaximin affects the colonic microbiota and its metabolism, an in vitro human colonic model system was used in this study.


METHODS
We investigated the impact of the administration of 1800 mg/day of rifaximin on the faecal microbiota of four patients affected by colonic active CD [Crohn's disease activity index (CDAI > 200)] using a continuous culture colonic model system. We studied the effect of rifaximin on the human gut microbiota using fluorescence in situ hybridization, quantitative PCR and PCR-denaturing gradient gel electrophoresis. Furthermore, we investigated the effect of the antibiotic on microbial metabolic profiles, using (1)H-NMR and solid phase microextraction coupled with gas chromatography/mass spectrometry, and its potential genotoxicity and cytotoxicity, using Comet and growth curve assays.


RESULTS
Rifaximin did not affect the overall composition of the gut microbiota, whereas it caused an increase in concentration of Bifidobacterium, Atopobium and Faecalibacterium prausnitzii. A shift in microbial metabolism was observed, as shown by increases in short-chain fatty acids, propanol, decanol, nonanone and aromatic organic compounds, and decreases in ethanol, methanol and glutamate. No genotoxicity or cytotoxicity was attributed to rifaximin, and conversely rifaximin was shown to have a chemopreventive role by protecting against hydrogen peroxide-induced DNA damage.


CONCLUSIONS
We demonstrated that rifaximin, while not altering the overall structure of the human colonic microbiota, increased bifidobacteria and led to variation of metabolic profiles associated with potential beneficial effects on the host.
Maccaferri
Simone
S
Department of Pharmaceutical Sciences, University of Bologna, Bologna, Italy.
Vitali
Beatrice
B
Klinder
Annett
A
Kolida
Sofia
S
Ndagijimana
Maurice
M
Laghi
Luca
L
Calanni
Fiorella
F
Brigidi
Patrizia
P
Gibson
Glenn R
GR
Costabile
Adele
A
D000890:Anti-Infective Agents / Q000494:pharmacology*; D001431:Bacteriological Techniques / Q000379:methods*; D001644:Bifidobacterium / Q000187:drug effects / Q000254:growth & development; D003106:Colon / Q000382:microbiology*; D003424:Crohn Disease / Q000382:microbiology*; D003470:Culture Media; D058645:Denaturing Gradient Gel Electrophoresis; D017753:Ecosystem; D005243:Feces / Q000382:microbiology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D054892:Metagenome / Q000187:drug effects*; D016133:Polymerase Chain Reaction; D012294:Rifamycins / Q000494:pharmacology*; D000078262:Rifaximin
D000890:Anti-Infective Agents; D003470:Culture Media; D012294:Rifamycins; D000078262:Rifaximin