title: The probiotic mixture VSL#3 accelerates gastric ulcer healing by stimulating vascular endothelial growth factor.
abstract: Studies assessing the effect and mechanism of probiotics on diseases of the upper gastrointestinal tract (GI) including gastric ulcers are limited despite extensive work and promising results of this therapeutic option for other GI diseases. In this study, we investigated the mechanisms by which the probiotic mixture VSL#3 (a mixture of eight probiotic bacteria including Lactobacilli, Bifidobacteria and Streptococcus species) heals acetic acid induced gastric ulcer in rats. VSL#3 was administered orally at low (6 × 10(9) bacteria) or high (1.2 × 10(10) bacteria) dosages from day 3 after ulcer induction for 14 consecutive days. VSL#3 treatments significantly enhanced gastric ulcer healing in a dose-dependent manner. To assess the mechanism(s) whereby VSL#3 exerted its protective effects, we quantified the gene expression of several pro-inflammatory cytokines, protein and expression of stomach mucin-Muc5ac, regulatory cytokine-IL-10, COX-2 and various growth factors. Of all the components examined, only expression and protein production of VEGF was increased 332-fold on day 7 in the ulcerated tissues of animals treated with VSL#3. Predictably, animals treated with VEGF neutralizing antibody significantly delayed gastric ulcer healing in VSL#3 treated animals. This is the first report to demonstrate high efficacy of the probiotic mixture VSL#3 in enhancing gastric ulcer healing. Probiotic efficacy was effective at higher concentrations of VSL#3 by specifically increasing the expression and production of angiogenesis promoting growth factors, primarily VEGF.
authors.affiliation: Department of Microbiology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Poonam
authors.initials: P
authors.lastname: Dharmani
authors.forename: Claudio
authors.initials: C
authors.lastname: De Simone
authors.forename: Kris
authors.initials: K
authors.lastname: Chadee
mesh_terms: D019342:Acetic Acid / Q000633:toxicity; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D006652:Histological Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D055271:Mucin 5AC / Q000378:metabolism; D009500:Neutralization Tests; D019936:Probiotics / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D016207:Cytokines; D017931:DNA Primers; D036341:Intercellular Signaling Peptides and Proteins; C524680:Muc5ac protein, rat; D055271:Mucin 5AC; D042461:Vascular Endothelial Growth Factor A; D019342:Acetic Acid