title: Probiotic E. coli treatment mediates antimicrobial human beta-defensin synthesis and fecal excretion in humans.
abstract: Inducible epithelial human beta-defensins (hBD) play an important role in intestinal barrier function. In vitro studies showed that clinically effective probiotics induce antimicrobial hBD-2. Here, we aimed to assess the in vivo effect in healthy volunteers and also addressed how defensins affect probiotic survival. Symbioflor 2 containing one strain of several viable genotypes of Escherichia coli was administered to 23 healthy individuals. After 3 weeks, fecal hBD-2 peptide was increased in 78% (mean 3.7-fold; P<0.0001). Interestingly, the fecal hBD-2 peptide was still elevated 9 weeks after treatment (P=0.008). In vitro studies revealed that this effect was mediated by only one out of three tested E. coli genotypes and comparable to probiotic E. coli Nissle 1917 (10- to 15-fold). Functional assays showed that all tested bacteria were similarly killed by defensins allowing to speculate about a suicidal character of this effect. Defensin induction seems to be a common and important mechanism of probiotic treatment.
authors.affiliation: Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology and University of Tübingen, Stuttgart, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Möndel
authors.forename: B O
authors.initials: BO
authors.lastname: Schroeder
authors.forename: K
authors.initials: K
authors.lastname: Zimmermann
authors.forename: H
authors.initials: H
authors.lastname: Huber
authors.forename: S
authors.initials: S
authors.lastname: Nuding
authors.forename: J
authors.initials: J
authors.lastname: Beisner
authors.forename: K
authors.initials: K
authors.lastname: Fellermann
authors.forename: E F
authors.initials: EF
authors.lastname: Stange
authors.forename: J
authors.initials: J
authors.lastname: Wehkamp
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018938:Caco-2 Cells; D004926:Escherichia coli / Q000187:drug effects / Q000502:physiology*; D005243:Feces / Q000737:chemistry*; D006801:Humans; D050296:Microbial Viability / Q000187:drug effects; D019936:Probiotics / Q000494:pharmacology* / Q000627:therapeutic use; D013045:Species Specificity; D023083:beta-Defensins / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; C106641:DEFB4A protein, human; D023083:beta-Defensins