Dietary probiotic and metabolites improve intestinal homeostasis and prevent colorectal cancer

Abstract

The excessive secretion of pro-inflammatory cytokines, uncontrolled cell proliferation, and dysbiosis in gut intestinal microbiota are involved in tumorigenesis and progression of colorectal cancer. Probiotics secrete various functional metabolites that maintain intestinal microflora balance and improve the host's gut health. This study defines the roles of dietary Lactobacillus (LC-CLA) metabolites, especially conjugated linoleic acids (CLA), in intestinal homeostasis. Based on cellular and transcriptional examination, LC-CLA cell free cultural supernatant (CFCS) significantly inhibited the viability of colorectal cancer cells (HCT-116). CFCSs containing various levels of CLA also significantly lowered the transcript levels of crucial genes for tumorous cell growth and proliferation, such as CDK1/2/6, PLK1, and SKP2. Furthermore, LC-CLA and its CFCS exhibited substantial free radical scavenging activities as well as downregulated pro-inflammatory cytokine and upregulated anti-inflammatory cytokine gene expressions. In addition, daily consumption of LC-CLA for one week modulated the composition of gut microflora by specifically reducing the relative abundance of sulfidogenic bacteria in mice. These findings reveal the potential application of CLA from probiotic origin as a dietary supplement or nutraceutical agent for improving gastrointestinal health and preventing colorectal cancer.