Dietary probiotic and metabolites improve intestinal homeostasis and prevent colorectal cancer.

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.

Limiting the pathogenesis of Salmonella Typhimurium with berry phenolic extracts and linoleic acid overproducing Lactobacillus casei.

The growing threat of emergent multidrug-resistant enteric bacterial pathogens, and their adopted virulence properties are directing to find alternative antimicrobials and/or development of dietaries that can improve host gut health and/or defense. Recently, we found that modified Lactobacillus casei (Lc + CLA) with increased production of conjugated linoleic acid has antimicrobial and other beneficial properties. Further, prebiotic alike products such as berry pomace extracts (BPEs), increase the growth of probiotics and inhibit the growth of certain bacterial pathogens. In this study, we evaluated the antibacterial effect of genetically modified Lc + CLA along with BPEs against major enteric pathogen Salmonella enterica serovar Typhimurium (ST). In mixed culture condition, the growth of ST was significantly reduced in the presence of Lc + CLA and/or BPEs. Bacterial cell-free cultural supernatant (CFCS) collected from wild-type Lc or modified Lc + CLA strains also inhibited the growth and survival of ST, and those inhibitory effects were enhanced in the presence of BPEs. We also found that the interaction of the pathogen with cultured host (HD-11 and INT-407) cells were also altered in the presence of either Lc or Lc + CLA strain or their CFCSs significantly. Furthermore, the relative expression of genes related to ST virulence and physicochemical properties of ST was altered by the effect of CFCSs of either Lc or Lc + CLA. These findings indicate that a diet containing synbiotic, specifically linoleic acid, over-produced Lc + CLA and prebiotic product BPEs, might have the potential to be effective in controlling ST growth and pathogenesis.