VSL#3 and conjugated linoleic acid ameliorate colitis and inflammation-driven colorectal cancer.

Abstract

e14108 Background: Inflammatory bowel disease (IBD) increases the risk of colorectal cancer. Manipulating the gut microbiota has been proposed to decrease inflammation and colorectal cancer. Bacterial species in the VSL#3 mixture are capable of producing conjugated linoleic acid (CLA), a polyunsaturated fatty acid with demonstrated anti-inflammatory and anti-carcinogenic effects. This study aimed to compare the anti-carcinogenic anti-inflammatory efficacies of dietary CLA versus VSL#3 treatment in mouse models of IBD and colon cancer. Methods: Following induction of colitis or inflammation-driven colorectal cancer mice treated with placebo, CLA or VSL#3 for 30 days were monitored for disease activity over time. Colonic specimens were collected for histopathology, gene expression and flow cytometric analyses. Immune cell subsets in the mesenteric lymph nodes (MLN), spleen, blood and colonic lamina propria lymphocytes (LPL) were phenotypically and functionally characterized. Results: VSL#3 and CLA ameliorated disease activity and reduced colonic inflammatory lesions and tumor formation, although VSL#3 was more effective than CLA. Histopathological examination revealed lower epithelial erosion, adenocarcinomas and adenomas in colons of VSL#3-treated mice when compared to the control and CLA groups, although CLA-treated mice had significantly lower tumors and leukocyte infiltration than controls. VSL#3 increased the percentage of interleukin 17 (IL-17) and FoxP3 expressing T cells in the MLN and colonic LPL, VSL#3 also increased the CD4+CD44+CD62L+ memory T cells population in the colonic LPL. Gene expression analyses showed that CLA reduced colonic mRNA expression of cyclooxygenase 2 (COX-2) and VSL#3 upregulated angiostatin expression. Conclusions: Both CLA and VSL#3 improved disease activity and reduced colonic inflammatory lesions and tumor formation in mouse models of IBD and inflammation-induced colorectal cancer, although VSL#3 showed greater anti-carcinogenic and anti-inflammatory activities than CLA. Mechanistically, CLA modulated expression of COX-2 levels in the colonic mucosa, whereas VSL#3 targeted regulatory mucosal CD4+ T cell responses.