STRUCTURAL CHANGE IN MICROBIOTA BY A PROBIOTIC COCKTAIL ENHANCES THE GUT BARRIER AND REDUCES CANCER VIA TLR2 SIGNALING IN A RAT MODEL OF COLON CANCER

Abstract

Background Structural change in the gut microbiota is implicated in cancer. The beneficial modulation of the microbiota composition with probiotics and prebiotics prevents diseases. Aim We investigated the effect of oligofructose–maltodex trin-enriched Lactobacillus acidophilus, Bifidobacteria bifi dum, and Bifidobacteria infantum (LBB), on the gut microbiota composition and progression of colorectal cancer. Methods Sprague Dawley rats were acclimatized, given ampicillin (75 mg/kg), and treated as follows; GCO: nor mal control; GPR: LBB only; GPC: LBB? 1,2-dimethyl hydrazine dihydrochloride (DMH); and GCA: DMH only (cancer control). 16S V4 Pyrosequencing for gut microbiota analysis, tumor studies, and the expression of MUC2, ZO-1, occludin, TLR2, TLR4, caspase 3, COX-2, and b-catenin were conducted at the end of experiment. Results Probiotic LBB treatment altered the gut micro biota. The relative abundance of genera Pseudomonas, Congregibacter, Clostridium, Candidactus spp., Phaeobacter, Escherichia, Helicobacter, and HTCC was decreased (P\0.05), but the genus Lactobacillus increased (P\0.05), in LBB treatment than in cancer control. The altered gut microbiota was associated with decreased tumor incidence (80 % in GPC vs. 100 % in GCA, P = 0.0001), tumor volume (GPC 84.23 (42.75–188.4) mm3 vs. GCA 243 (175.5–344.5) mm3 , P\0.0001) and tumor multiplicity/count (GPC 2.92 ± 0.26 vs. GCA 6.27 ± 0.41; P\0.0001). The expression of MUC2, ZO-1, occludin, and TLR2 was increased, but expression of TLR4, caspase 3, Cox-2, and b-catenin was decreased by LBB treatment than in cancer control GCA (P\0.05). Conclusion Administration of LBB modulates the gut microbiota and reduces colon cancer development by decreasing tumor incidence, multiplicity/count, and volume via enhanced TLR2-improved gut mucosa epithelial barrier integrity and suppression of apoptosis and inflammation.