title: Pretreatment with the probiotic VSL#3 delays transition from inflammation to dysplasia in a rat model of colitis-associated cancer.
abstract: Evidence supports involvement of microflora in the transition of chronic inflammation to neoplasia. We investigated the protective efficacy of the probiotic VSL#3 in a model of colitis-associated colorectal cancer. Chronic colitis was induced in Sprague-Dawley rats by administration of trinitrobenzene sulfonic acid (TNBS), followed 6 wk later by systemic reactivation. To induce colitis-associated dysplasia and cancer, the animals received TNBS (intravenously) twice a week for 10 wk. One group received VSL#3 in drinking water from 1 wk before colitis induction until death. The colons were examined for damage and presence of dysplasia or cancer. Samples were analyzed for cell proliferation and apoptosis, vitamin D receptor (VDR) expression, angiogenic factors, and presence of alkaline sphingomyelinase or phosphatase. Microbial community composition was evaluated by terminal restriction fragment-length polymorphism analysis of the bacterial 16S rRNA gene. None of the probiotic-treated animals developed carcinoma, and no high-grade dysplasia was found in either the proximal or mid colon. In contrast, 29% of the animals in the control group developed carcinoma in one or more regions of the colon. VSL#3-treated animals had significantly less damage than the vehicle treated-controls in all areas of the colon, and this correlated with decreased richness and diversity of the mucosally adherent microbiota. Treatment with the probiotic increased the antiangiogenic factor angiostatin, VDR expression, and alkaline sphingomyelinase. We concluded that pretreatment with the probiotic VSL#3 can attenuate various inflammatory-associated parameters, delaying transition to dysplasia and cancer, thus offering its potential therapeutic use in patients with long-standing colitis.
authors: Dept. of Physiology and Pharmacology, Ponce School of Medicine, PO Box 7004, Ponce, Puerto Rico 00732-7004. cappleyard@psm.edu
authors: Caroline B
authors: CB
authors: Appleyard
authors: Myrella L
authors: ML
authors: Cruz
authors: Angel A
authors: AA
authors: Isidro
authors: Janelle C
authors: JC
authors: Arthur
authors: Christian
authors: C
authors: Jobin
authors: Claudio
authors: C
authors: De Simone
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D043168:Angiostatins / Q000378:metabolism; D000818:Animals; D001644:Bifidobacterium; D002908:Chronic Disease; D003092:Colitis / Q000276:immunology / Q000382:microbiology / Q000628:therapy*; D003106:Colon / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D015179:Colorectal Neoplasms / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D004195:Disease Models, Animal; D043169:Endostatins / Q000378:metabolism; D007778:Lactobacillus; D008297:Male; D054892:Metagenome; D011230:Precancerous Conditions / Q000276:immunology / Q000382:microbiology / Q000628:therapy*; D019936:Probiotics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018167:Receptors, Calcitriol / Q000378:metabolism; D013291:Streptococcus; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D043169:Endostatins; D018167:Receptors, Calcitriol; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D043168:Angiostatins; D000469:Alkaline Phosphatase