Genotoxicity of Escherichia coli Nissle 1917 strain cannot be dissociated from its probiotic activity.
Oral administration of the probiotic bacterium Escherichia coli Nissle 1917 improves chronic inflammatory bowel diseases, but the molecular basis for this therapeutic efficacy is unknown. E. coli Nissle 1917 harbors a cluster of genes coding for the biosynthesis of hybrid nonribosomal peptide-polyketide(s). This biosynthetic pathway confers the ability for bacteria to induce DNA double strand breaks in eukaryotic cells. Here we reveal that inactivation of the clbA gene within this genomic island abrogated the ability for the strain to induce DNA damage and chromosomal abnormalities in non-transformed cultured rat intestinal epithelial cells but is required for the probiotic activity of E. coli Nissle 1917. Thus, evaluation of colitis severity induced in rodent fed with E. coli Nissle 1917 or an isogenic non-genotoxic mutant demonstrated the need for a functional biosynthetic pathway both in the amelioration of the disease and in the modulation of cytokine expression. Feeding rodents with a complemented strain for which genotoxicity was restored confirmed that this biosynthetic pathway contributes to the health benefits of the probiotic by modulating its immunomodulatory properties. Our data provide additional evidence for the benefit of this currently used probiotic in colitis but remind us that an efficient probiotic may also have side effects as any other medication.
Neuro-gastroenterologie et Nutrition, UMR INRA/ENVT 1331, Toulouse, France. maiwenn.olier@toulouse.inra.fr
Maïwenn
M
Olier
Ingrid
I
Marcq
Christel
C
Salvador-Cartier
Thomas
T
Secher
Ulrich
U
Dobrindt
Michèle
M
Boury
Valérie
V
Bacquié
Marie
M
Pénary
Eric
E
Gaultier
Jean-Philippe
JP
Nougayrède
Jean
J
Fioramonti
Eric
E
Oswald
D000818:Animals; D002460:Cell Line; D003092:Colitis / Q000382:microbiology; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D055786:Gene Knockout Techniques; D015212:Inflammatory Bowel Diseases / Q000628:therapy*; D008297:Male; D009153:Mutagens / Q000378:metabolism*; D061065:Polyketides / Q000378:metabolism; D019936:Probiotics / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar
D009153:Mutagens; D061065:Polyketides