Toward understanding the metabolic and genotoxic effect of gut microbiota-derived metabolites on colonic epithelial cells
Implementing Organization
National Institute of Immunology (NII)
Principal Investigator
Dr. Shikha Solanki
National Institute Of Immunology
solankishikha3012@gmail.com
Project Overview
Based on recent research reports, dysbiosis and improper concentrations of microbial metabolites in the gut may results into the carcinogenesis of colorectal cancer. Gut microbial metabolites are functional output of the host-microbiota interactions and produced by anaerobic fermentation of food components in the diet. They contribute to influence variety of biological mechanisms including inflammation, cell signaling, cell cycle disruption which are majorly disrupted in carcinogenic activities. Current evidences have proposed the role of bacteria such as Fusobacterium nucleaturm, Streptococcus bovis, Helicobacter pylori, Bacteroides fragilis and Clostridium septicum in the carcinogenesis of CRC. These bacteria produce metabolites, such as secondary bile salts from primary bile salts, indoxyl sulphate, para-cresol sulphate, hydrogen sulphide, trimethylamine-N-oxide (TMAO) which are likely to promote inflammation and subsequently cancer development. There are studies which suggest that gut microbiota derived metabolites have a role in CRC progression and causation and hence, could be implicated in CRC diagnosis, prognosis and therapy. So, in this work, we will study the effect of these bacterial metabolites i.e. Glycocholic acid and Hippuric Acid on gut normal epithelial cell line (CCD841) and adenocarcinoma cell lines (HCT-116 and HT-29). Different assays will be performed for checking the genotoxicity of these metabolites. Cells will be seeded and then treated with these metabolites and after treatment of various time periods, cell viability assay, cell titer assay, LDH assay, apoptosis assay, cell cycle assay. comet assay, colonogenic assay, cell proliferation assay will be performed for checking the effect of these metabolites. The evaluation of screened and validated microbial metabolites for colon cancer treatment using two mice models will also be done.
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