Pretreatment of Probiotic Bifico Ameliorates Colitis-Associated Cancer in Mice: Transcriptome and Gut Flora Profiling

Abstract

Individuals with inflammatory bowel disease (IBD) are at a high risk for developing colitis-associated cancer (CAC). Strategies to block the process from IBD to CAC should be considered. In the experiment, we aim to explore the chemopreventive efficacy of the probiotic cocktail Bifico and its potential mechanism in azoxymethane (AOM) and dextran sodium sulphate (DSS) induced colitis-associated cancer in mice. Oral pretreatment of Bifico was adopted to evaluate its protective effect. The colorectums of thirty-five C57BL/6 mice were collected and examined for degree of inflammation and tumorigenesis. Methods of cDNA microarray, comparative 16S rRNA sequencing were performed to observe Bifico-target alterations in gene expression and microbiota structure. We found pretreatment of Bifico alleviated intestinal inflammation and reduced tumor formation. Furthermore, we identified a subset of genes as potential targets of Bifico treatment, including chemokine C-X-C motif ligand 1 (CXCL1), CXCL2, CXCL3, and CXCL5, which were all ligands of C-X-C motif receptor 2 (CXCR2). 16S rRNA sequencing demonstrated that Bifico decreased the abundance of genus Desulfovibrio, Mucispirillum and Odoribacter, while a bloom of genus Lactobacillus was detected. Notably, we found abundance of these Bifico-target taxa was significantly associated with the expression of CXCR2 ligand genes. Our studies demonstrate that oral administration of Bifico can ameliorate CAC in mice through intervening with the possible link between Desulfovibrio, Mucispirillum, Odoribacter, Lactobacillus and CXCR2 signaling.

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