ABSTRACT
Prebiotics modulate microbial composition and ensure a healthy gastrointestinal tract environment that can prevent colon cancer development. These natural dietary compounds are therefore potential chemopreventive agents. Thirty Sprague-Dawley rats (4 months old) were experimentally treated with procarcinogen dimethylhydrazine to induce colon cancer development. The rats were randomly assigned to three groups: a control group (CG), a group treated with dimethylhydrazine (DMH), and a group given DMH and inulin, a prebiotic (DMH+PRE). The effects of inulin on the activities of bacterial glycolytic enzymes, short-chain fatty acids, coliform and lactobacilli counts, cytokine levels, and cyclooxygenase-2 (COX-2) and transcription nuclear factor kappa beta (NFkappaB) immunoreactivity were measured. Inulin significantly decreased coliform counts (p < 0.01), increased lactobacilli counts (p < 0.001), and decreased the activity of beta-glucuronidase (p < 0.01). Butyric and propionic concentrations were decreased in the DMH group. Inulin increased its concentration that had been reduced by DMH. Inulin decreased the numbers of COX-2- and NFkappaB-positive cells in the tunica mucosae and tela submucosae of the colon. The expression of IL-2, TNFalpha, and IL-10 was also diminished. This 28-week study showed that dietary intake of inulin prevents preneoplastic changes and inflammation that promote colon cancer development.
Subject(s)
Animals , Female , Male , Rats , Bacterial Proteins/genetics , Colon/enzymology , Colonic Neoplasms/chemically induced , Colony Count, Microbial , Cyclooxygenase 2/genetics , Cytokines/blood , Diet , Dietary Supplements/analysis , Dimethylhydrazines/toxicity , Enterobacteriaceae/drug effects , Fatty Acids, Volatile/genetics , Gene Expression Regulation/drug effects , Inulin/administration & dosage , Lactobacillaceae/drug effects , NF-kappa B/genetics , Prebiotics/analysis , Rats, Sprague-DawleyABSTRACT
Salmonella enterica serovar typhimurium (S. typhimurium) encounters short chain fatty acids (inorganic acids containing propionate, butyrate and acetate) in the intestine as well as in food preservatives. Short chain fatty acids (SCFAs) exposed organisms have been reported to offer resistance to organic acid resulting into enhanced virulence. However, the role of hilA (hyper invasive loci) gene expression has not been assessed in this context. In the present study, S. typhimurium was grown under SCFAs stress condition simulating the in vivo environment and hilA gene expression was evaluated. The gene expression was measured by beta-galactosidase (beta-gal) assay using a hilA-lacZY fusion strain and calculated as Miller units. hilA gene expression was found to be significantly higher in the SCFAs exposed cells than the unexposed ones, after 2 hrs and 4 hrs of exposure. However, no significant difference was observed between the activities at 2 hrs and 4 hrs. It indicates that hilA gene gets expressed by 2 hrs and persists till 4 hrs at least. The beta-gal activity was also measured in the unadapted / SCFAs adapted organisms followed by acid shock for 1 hr. The gene expression was also found to be higher in the SCFAs adapted--acid (pH 3) challenged as compared to the unadapated acid challenged organisms suggesting that SCFAs adaptation may induce organic acid tolerance by modulating the hilA response. This observation indicates that hilA may be the additional gene contributing to acid resistance and thereby increasing virulence of the organism after SCFAs adaptation.